Polynucleotide probe and primer originating in hepatitis e virus of japanese, chips having the same, kits having the same and method of detecting hepatits e virus using the same

ABSTRACT

A polynucleotide probe including a sequence comprising at least eight nucleotides, the polynucleotide probe being used for detecting polynucleotide of hepatitis E virus, is characterized in that the sequence comprising at least eight nucleotides is hybridized with the polynucleotide of the hepatitis E virus, thereby, due to the hybridization, detects the hepatitis E virus.

TECHNICAL FIELD

[0001] The present invention relates to a novel method for detectinghepatitis E virus. The present invention also relates to a novel strainof hepatitis E virus recovered from Japanese, a novel strain ofhepatitis E virus from a patient with fulminant hepatitis, andpolynucleotide derived therefrom, which is important for establishingthe novel method for detecting the RNA genome of hepatitis E virus.

BACKGROUND ART

[0002] Hepatitis E virus (which will be referred to as “HEV”hereinafter) which replicates in the liver of a patient is voided tofeces rather than staying in blood. Accordingly, HEV is transmittedmainly by feco-oral route. Thus, HEV infection sometimes happens as alocal outbreak caused by contamination of a water system. Due to such amanner of infection, hepatitis E caused by HEV is frequently observed inregions where the sanitary environment is not satisfactory, such as Asiaand Africa. On the contrary, HEV infection is relatively rare in theindustrially advanced countries such as Japan, US and Europe. Most ofthe hepatitis E cases, which are occasionally reported in these advancedcountries, are found in travelers who have been to the regions where thedisease is endemic and recently come back to their own countries.Accordingly, hepatitis E is generally recognized in the advancedcountries as an “imported disease”.

[0003] HEV was genetically cloned by Reyes of Genelabs Co., in theUnited States, in 1990, for the first time. The entire nucleotidesequence of the HEV genome was then revealed by the study thereafter.The HEV strains whose full-genome sequence had been analyzed were whatis called the “Mexico” strain and the “Burma” strain. Thereafter, thesequences of the genomes derived from the “India” strain, the “Pakistan”strain, the “Nepal” strain, the “Burma” strain, the “China” strain, the“US” strain and the like have been sequentially been revealed. However,the nucleotide sequence of the HEV gene derived from the “Japan” strainhas not been revealed yet.

[0004] The conventional method of diagnosing HEV infection includes: amethod of conducting a PCR method by using a primer designed on thebasis of the nucleotide sequences of the aforementioned various knownHEV strains, for detecting the RNA genome of the virus; and a method ofusing, as an antigen, a peptide/protein which has beensynthesized/expressed on the basis of the amino acid sequence of theknown HEV strains, for detecting an antibody specific thereto.

[0005] In the conventional method or technique of diagnosing HEVinfection, if an unknown HEV strain having a line different from theknown HEV strains exists in the sample to be tested, there is asignificant possibility that the unknown virus cannot be detected.

DISCLOSURE OF INVENTION

[0006] An object of the present invention is to provide a method whichenables “wide-range” detection of HEV belonging to various strains.Another object of the present invention is to provide polynucleotide forwidely detecting HEV belonging to various strains and polynucleotide fordetermining the strain of the detected HEV.

[0007] Yet another object of the present invention is to providepolynucleotide derived from a novel HEV strain endemic to Japan,polynucleotide derived from a novel strain of fulminant HEV, andpolypeptides coded by these nucleotide sequences.

[0008] A further object of the present invention is to provide a methodfor carrying out a drug design, which drug design is achieved byutilizing the genetic information of the novel HEV described above andthe genetic information of the conventional known HEV.

[0009] The inventors of the present invention have molecularly isolated,for the first time in the world, the HEV strains (specifically the HEVJapan JRA1 strain, the JKN-Sap strain, the JMY-Haw strain, JKK-Sapstrain and JAK-Sai strain) from Japanese patients, isolated HEV JapanJSN-FH strain as a novel HEV strain from a case of fulminant hepatitis,and determined the genome sequence of the obtained virus. The presentinvention has been achieved on the basis of these discoveries.

[0010] According to a first aspect of the present invention, there isprovided a polynucleotide probe including a sequence comprising at leasteight nucleotides, the polynucleotide probe being used for detecting thegenomic polynucleotide of hepatitis E virus, characterized in that:

[0011] (1) the sequence comprising at least eight nucleotides ishybridized with the polynucleotide of the hepatitis E virus, thereby,due to the hybridization, detecting the hepatitis E virus; and

[0012] (2) the sequence comprising at least eight nucleotides isobtained from a sequence selected from the group consisting ofnucleotide sequences disclosed at SEQ No. 11, SEQ No. 44, SEQ No. 45,SEQ No. 46, SEQ No. 47 and SEQ No. 48 and complementary strands thereof.

[0013] According to a second aspect of the present invention, there isprovided a pair or plural pairs of primer for PCR for amplifyingpolynucleotide of hepatitis E virus, the at least a pair of primer forPCR each independently having a sequence comprising at least eightnucleotides, characterized in that:

[0014] (1) the sequence comprising at least eight nucleotides ishybridized with the genomic polynucleotide of the hepatitis E virus,thereby, due to the hybridization, amplifying a portion of thepolynucleotide of the hepatitis E virus; and

[0015] (2) the sequence comprising at least eight nucleotides isobtained from a sequence selected from the group consisting ofnucleotide sequences disclosed at SEQ No. 11, SEQ No. 44, SEQ No. 45,SEQ No. 46, SEQ No. 47 and SEQ No. 48 and complementary strands thereof.

[0016] According to a third aspect of the present invention, there isprovided a method of detecting presence of hepatitis E virus in asample, comprising:

[0017] (1) obtaining a sample from an object;

[0018] (2) reacting the sample obtained in the obtaining of (1) with thepolynucleotide probe according to the first aspect;

[0019] (3) detecting a double strand produced as a result of thereaction of the reacting of (2);

[0020] (4) determining whether or not hepatitis E virus is present inthe sample, on the basis of the detection result of the detecting of(3).

[0021] According to a fourth aspect of the present invention, there isprovided a method for detecting presence of hepatitis E virus in asample, comprising:

[0022] (1) obtaining a sample from an object;

[0023] (2) reacting the sample obtained in the obtaining of (1) with apair of primer for PCR according to the second aspect and polymerase,under a condition in which amplification is effected in an appropriatemanner;

[0024] (3) detecting presence of a product obtained as a result ofamplification by the reaction of the reacting of (2);

[0025] (4) determining whether or not hepatitis E virus is present inthe sample, on the basis of the detection result of the detecting of(3).

[0026] According to a fifth aspect of the present invention, there isprovided a method for determining genotype of hepatitis E virus in asample, comprising:

[0027] (1) reacting a sample with a pair of primer for PCR according toclaim 12 and polymerase, under a condition in which amplification iseffected in an appropriate manner;

[0028] (2) determining length of a product obtained as a result ofamplification by the reaction of the reacting of (1);

[0029] (3) determining genotype of hepatitis E virus present in thesample, on the basis of the detection result of the determining of (2).

[0030] According to a sixth aspect of the present invention, there isprovided a probe assay kit, including the polynucleotide probe accordingto the first aspect.

[0031] According to a seventh aspect of the present invention, there isprovided a PCR assay kit, including the pair or plural pairs of primerfor PCR according to the second aspect.

[0032] According to an eighth aspect of the present invention, there isprovided a chip for detecting a nucleotide sequence, on which thepolynucleotide probe according to the first aspect has been immobilized.

BRIEF DESCRIPTION OF DRAWINGS

[0033]FIG. 1 s a view showing a phylogenetic tree of a hepatitis E virusstrain.

[0034]FIG. 2 is a view showing a genetic organization of HEV JRA1.

[0035]FIG. 3A and FIG. 3B are views showing a portion of the nucleotidesequence of HEV JRA1 and a portion of the nucleotide sequence of the“Mexico” strain in a manner that the former is compared with the latter.

[0036]FIG. 4A and FIG. 4B are, in addition to FIGS. 3A and 3B, viewsshowing a portion of the nucleotide sequence of HEV JRA1 and a portionof the nucleotide sequence of the “Mexico” strain in a manner that theformer is compared with the latter.

[0037]FIG. 5B and FIG. 5B, in addition to FIGS. 4A and 4B, views showinga portion of the nucleotide sequence of HEV JRA1 and a portion of thenucleotide sequence of the “Mexico” strain in a manner that the formeris compared with the latter.

[0038]FIG. 6 is a view showing a primer and a probe according toembodiments of the present invention.

[0039]FIG. 7 is a view showing a portion of the nucleotide sequence ofHEV JSN-FH and a portion of the nucleotide sequence of the “Mexico”strain in a manner that the former is compared with the latter.

[0040]FIG. 8 is, in addition to FIG. 7, a view showing a portion of thenucleotide sequence of HEV JSN-FH and a portion of the nucleotidesequence of the “Mexico” strain in a manner that the former is comparedwith the latter.

[0041]FIG. 10 is, in addition to FIG. 8, a view showing a portion of thenucleotide sequence of HEV JSN-FH and a portion of the nucleotidesequence of the “Mexico” strain in a manner that the former is comparedwith the latter.

[0042]FIG. 10 is, in addition to FIG. 9, a view showing a portion of thenucleotide sequence of HEV JSN-FH and a portion of the nucleotidesequence of the “Mexico” strain in a manner that the former is comparedwith the latter.

[0043]FIG. 11 is, in addition to FIG. 10, a view showing a portion ofthe nucleotide sequence of HEV JSN-FH and a portion of the nucleotidesequence of the “Mexico” strain in a manner that the former is comparedwith the latter.

[0044]FIG. 12 is, in addition to FIG. 11, a view showing a portion ofthe nucleotide sequence of HEV JSN-FH and a portion of the nucleotidesequence of the “Mexico” strain in a manner that the former is comparedwith the latter.

[0045]FIG. 13 is a view showing the ORF regions of various HEV strainsin a manner that the ORF regions are compared with one another.

[0046]FIG. 14 is a view showing a phylogenetic tree of the HEV strain.

[0047]FIG. 15 is a view showing the sequence of the ORF1 of various HEVstrains in a manner that the ORF1 regions are compared with one another.

[0048]FIG. 16 is, in addition to FIG. 15, a view showing the sequence ofthe ORF1 of various HEV strains in a manner that the ORF1 regions arecompared with one another.

[0049]FIG. 17 is, in addition to FIG. 16, a view showing the sequence ofthe ORF1 of various HEV strains in a manner that the ORF1 regions arecompared with one another.

[0050]FIG. 18 is, in addition to FIG. 17, a view showing the sequence ofthe ORF1 of various HEV strains in a manner that the ORF1 regions arecompared with one another.

[0051]FIG. 19 is a view showing the data which indicates the presence ofRNA of HEV in a serum sample collected from a patient, which data isshown combined with changes in the liver function test values.

[0052]FIG. 20 is a chart showing results of HEV detection, obtained fromsamples of patients of non A, B, C acute hepatitis by using the primeraccording to embodiments of the present invention.

[0053]FIG. 21 is a chart showing results of HEV detection, which wassuccessively conducted for a patient, according to embodiments of thepresent invention.

[0054]FIG. 22 is a view showing a result of detection of the amplifiedHEV genome by electrophoresis, according to embodiments of the presentinvention.

[0055]FIGS. 23A to 23E are views showing the relationship between thetypes of a probe, the genotype of HEV and absorbance.

BEST MODE FOR CARRYING OUT THE INVENTION I. Terms

[0056] The term “polynucleotide” used in the present specificationinclusively represents, for convenience, polynucleotide, oligonucleotideand the like. Further, the term “polynucleotide” used in the presentspecification represents a substance resulted from phosphoricester-bonding of no less than two nucleoside. Nucleoside generallyincludes deoxyribonucleoside and ribonucleoside, without being limitedthereto. “Oligonucleotide” represents a substance obtained bypolymerizing, by means of phosphodiester bonding, phosphoric esters of afew to dozens of nucleoside (i.e., nucleotide). Oligonucleotidegenerally includes oligoribonucleotide and oligodeoxyribonucleotide,without being limited thereto. The polynucleotide according toembodiments of the present invention may be either virus-genome RNArecovered from the HEV JRA1 strain or DNA (or the like) obtained fromthe virus-genome RNA. Further, “polynucleotide” of the present inventionmay include artificially synthesized nucleic acid such as peptidenucleic acid, morpholino nucleic acid, methylphosphonate nucleic acidand S-oligo nucleic acid.

[0057] The “polypeptide” used in the present specification generallyrepresents a peptide composed of no less than two amino acids, anoligopeptide or a protein. The “polypeptide” used in the presentspecification includes both synthesized peptide and expressed protein,without being limited thereto. The “polypeptide” may be either a simpleprotein composed of only amino acids or a composite protein containingcomponents other than amino acids.

[0058] The term “object” used in the present specification may be one ofany mammal or the like, including human, dog, cat, cow, goat, pig, sheepand monkey. In the present embodiment, a human is the most suitableobject.

[0059] The term “sample” used in the present specification represents abiosample such as blood, serum, stool, liver and lymph, collected froman individual or biont as the object. The “sample” of the presentinvention may also be obtained by subjecting a biosample to anynecessary preparatory treatment such as homogenization, extraction orthe like. Such a preparatory treatment will be easily selected by oneskilled in the art, in accordance with the biosample used as the object.

[0060] The term “open reading frame” used in the present specificationrepresents a region of a polynucleotide sequence which codes apolypeptide. This region represents at least a portion of the codingsequence.

[0061] The term “hepatitis E virus” used in the present specificationrepresents the virus as the primary cause of epidemic non-A, non-Bhepatitis, which spreads by the medium of drinking water, is transmittedby way of digestive tract and is observed mainly in Asia and Africa. Thehepatitis E virus is RNA virus and classified into genus calicivirus ofthe family caliciviridae. The term “HEV” used in the presentspecification comprehensively represents a virus belonging to thegenotypes I, II, III and IV, commonly used for virus classification.Further, according to embodiments the present invention, any strainwhich belongs to HEV and has not been isolated/identified can bedetected and/or identified or classified into a genotype. Accordingly,the term “HEV” used in the present specification can include an unknownHEV and a virus which is detected and/or identified or classified into agenotype according to embodiments the present invention. “HEV” in thepresent specification includes a wild type, a variant, and a strainwhich is genetically close to HEV. Specifically, “HEV” in the presentspecification represents a strain which shows homology of approximately50% or more, preferably 60% or more, and most preferably 65% or more,with respect to the sequence of approximately 2500 nucleotides on the 5′end side of JRA1 shown in Sequence No. 1.

II. Strain of Novel Hepatitis E Virus

[0062] The inventors of the present invention have assumed that an HEVstrain which is indigenous to Japan does exist, on the basis of the factthat hepatitis E cases have been observed in Japan even among those whohave never been abroad, although the number of these cases is relativelysmall. Under this assumption, the inventors of the present inventionhave attempted cloning of HEV genomes recovered from Japanese patientswho developed acute hepatitis and, as a result, succeeded in isolatingfive HEV strains which appear to belong to a novel line.

[0063] These novel HEV strains are five strains named as follows by theinventors: HEV Japan JRA1 strain (Hepatitis E virus Japan JRA1, alsoreferred to as “JRA1 strain” hereinafter, NCBI accession No. AP003430);HEV Japan JKN-Sap strain (Hepatitis E virus Japan JKN-Sap, also referredto as “JKN-Sap strain” hereinafter, NCBI accession No. AB074918); HEVJapan JMY-Haw strain (Hepatitis E virus Japan JMY-Haw, also referred toas “JMY-Haw strain” hereinafter, NCBI accession No. AB074920); HEV JapanJKK-Sap strain (Hepatitis E virus Japan JKK-Sap, also referred to as“JKK-Sap strain” hereinafter, NCBI accession No. AB074917); and HEVJapan JAK-Sai strain (Hepatitis E virus Japan JAK-Sai, also referred toas “JAK-Sai strain” hereinafter, NCBI accession No. AB074915). Withregards to the origin of each virus strain, JKK-Sap, JKN-Sap and JMY-Hawwere derived from acute hepatitis E patients from Hokkaido, JAK-Sai isderived from an acute hepatitis E patient from Saitama prefecture, andJRA1 is derived from a patient from Tokyo.

[0064] Further, the inventors of the present invention have cloned theHEV JSN-FH strain (Hepatitis E virus JSN-FH, which will occasionally bereferred to as “JSN-FH strain”) as a novel HEV strain from a fulminanthepatitis case.

[0065] Open reading frame 1 (which will be referred to as “ORF1”hereinafter) of the genome RNA sequence of JRA1 strain is shown at thesequence (SEQ) No. 1, and the whole length of this genome RNA sequenceis shown at the SEQ No. 48.

[0066] The semi-whole length of the genome RNA sequence of JSN-FHstrain, which does not include a portion of non-coding sequence at the5′ end side of the genome RNA sequence, is shown at the SEQ No. 11. Theamino acid sequences which are coded in ORF1 and ORF 2 of the genome RNAsequence of JSN-FH strain are shown at the SEQ No. 12 and the SEQ No.13, respectively.

[0067] A portion of ORF1 of the genome RNA sequence of each of JKN-Sapstrain, JMY-Haw strain, JAK-Sai strain and JKK-Sap strain is shown atthe SEQ No. 16, the SEQ No. 17, the SEQ No. 20 and the SEQ No. 21,respectively. Further, the whole length of the genome RNA sequence ofeach of JKN-Sap strain, JMY-Haw strain, JAK-Sai strain and JKK-Sapstrain is shown at the SEQ No. 44, the SEQ No. 45 (the semi-wholelength), the SEQ No. 46 (the semi-whole length) and the SEQ No. 47 (thesemi-whole length), respectively.

2. HEV JRA1 Strain (1) HEV JRA1 Strain

[0068] The inventors of the present invention have revealed that thenucleotide sequence of JRA1 strain disclosed at the SEQ No. 1 belongs toa novel genotype, as compared with the known strains of various typescollected from various areas in the world, as shown in the phylogenetictree of FIG. 1.

[0069] The difference in nucleotide sequence between the known strainsand JRA1 strain is particularly obvious in the approximately 2500nucleotides at the genome 5′ end. As shown in FIG. 2, the hepatitis Evirus genome, including HEV-JRA1, generally contains three open readingframes (which will be referred to as “ORF” hereinafter) of ORF1, ORF2and ORF3. The approximately 5000 nucleotides at the 5′ end is includedto ORF1. The genome regions at the downstream side of ORF1, i.e., theother regions including the ORF2 region and the ORF3 region exhibitrelatively high sequence-conservation between strains, as compared withthe ORF1 region.

[0070] The sequence of the approximately 2500 nucleotides at the 5′ end,in particular, in the ORF1 region exhibits, regarding the portion of thenucleotide sequence of JRA1 strain shown at the SEQ No. 7 of thesequence list described below, degree of homology (of sequence) of only70% or less, as compared with the “Mexico” strain (SEQ ID NO-10 of U.S.Pat. No. 5,789,559, NCBI accession No. M74506, shown at the SEQ No. 49)which still shows the highest homology to JRA1 among the nucleotidesequence disclosed in the patents owned by Reyes. The nucleotidesequences of JRA1 strain and the “Mexico” strain are shown in FIGS. 3A,3B, 4A, 4B, 5A and 5B in a manner that the former is compared with thelatter. In FIGS. 3A, 3B, 4A, 4B, 5A and 5B, the sequence of HEV-JRA1strain and a portion of the sequence of the “Mexico” strain are shown ina juxtaposed manner so that the former is shown as the upper sequenceand the latter is shown as the lower sequence. The homology between thetwo sequences is 69.9% per 2432 nucleotides.

[0071] Accordingly, as such a specific novel sequence as described aboveof JRA1 strain has been revealed, JRA1 strain, which has never beensubjected to detection and thus never been properly detected, can now bedetected in an easy and accurate manner. Further, it is expected thatthe strains which are genetically close to JRA1 strain, which havehardly been detected by the conventional method, can also be detected bythe present invention. Description will now be given of the embodimentsof the present invention regarding the determination of the novel genomesequence of the novel hepatitis E virus strain described above.

(2) Polynucleotide

[0072] In one embodiment of the present invention, a polynucleotidewhich is specific to JRA1 strain and has a novel sequence is provided.The polynucleotide of the present embodiment may be, for example, apolynucleotide shown as a nucleotide sequence of the SEQ No. 1containing 5138 nucleotides. Alternatively, the polynucleotide may be apolynucleotide fragment, as a nucleotide sequence of any of the regionsof the SEQ No. 1 nucleotide sequence. Specifically, the polynucleotidemay be a polynucleotide shown as the nucleotide sequence of SEQ No. 7containing 2442 nucleotides, or, a complementary strand of any one ofthe nucleotide sequences described above. Or, the polynucleotide of thepresent embodiment may be a polynucleotide fragment as a nucleotidesequence which constitutes a portion of any one of the aforementionedpolynucleotides and the complementary strands thereof.

[0073] One or a few nucleotides of each polynucleotide described abovemay be subjected to modification such as deletion, substitution oraddition.

[0074] In another embodiment of the present invention, a primer and aprobe each constituted of any one of the nucleotide sequences of the SEQNos. 1 to 7 or the complementary strand thereof or a polynucleotidefragment having a fragment of any one of the nucleotide sequences of theSEQ Nos. 1 to 7 and the complementary strand thereof, are provided. Theprimer and probe may be used as a primer for amplification for detectingHEV in the detection object (for example, as a primer for PCRamplification or the like), or as a probe used in a “DNA chip”. In thiscase, the number of nucleotides contained in the polynucleotide of thepresent embodiment is preferably in a range of 10 to 30 (inclusive ofboth 10 and 30). If the length of the polynucleotide fragment is toolong, it is difficult to recognize the difference between the fragments,as the difference could be one nucleotide. If the length of thepolynucleotide is too short, it is difficult to determine the nucleotidesequence of polynucleotide contained in the sample.

[0075] Examples of the primer and the probe of the present embodiment asdescribed above include those for comprehensively detecting HEV and forselectively detecting each genotype of HEV.

[0076]FIG. 6 shows a portion of the nucleotide sequence information ofJRA1 strain and the nucleotide sequence information of known strains atthe corresponding site, in a juxtaposed manner, so that the former iscompared with the latter. By comparing the nucleotide sequence of JRA1strain with the nucleotide sequence of known strains at thecorresponding site, as shown in the example of FIG. 6, it is possible toclearly identify a highly-conserved region useful for setting aprimer/probe for comprehensively detecting HEV and a highly-mutatedregion for selectively detecting each genotype of HEV.

[0077] The term “highly-conserved region” used in the present inventionindicates a region which exhibits high homology, e.g., 90% or more,preferably 95% or more, and most preferably 100% of homology between thenucleotide sequence of HEV-JRA1 strain and the corresponding nucleotidesequence of a known strain. The term “highly-mutated region” used in thepresent specification indicates a region which is a nucleotide sequencespecific to HEV-JRA1 strain and exhibits relatively low homology, e.g.,80% or less, preferably 75% or less, and most preferably 70% or less ofhomology between the nucleotide sequence of HEV-JRA1 strain and thecorresponding nucleotide sequence of a known strain.

[0078]FIG. 6 shows the 111^(th) nucleotide to the 124^(th) nucleotide ofthe SEQ No. 1 of HEV-JRA1 strain as an example of a “candidate” regionfor setting a primer and a probe for comprehensively detecting HEV, andthe region corresponding thereto of known strains. The polynucleotideshown as the nucleotide sequences of the SEQ Nos. 2 to 5 or thecomplementary strand of any one of the nucleotide sequences of the SEQNos. 2 to 5, for example, can be used as a primer and a probe forcomprehensively detecting HEV. On the other hand, the region of the SEQNo. 1 which can be used as a primer and a probe for comprehensivelydetecting HEV is not limited thereto.

[0079] Similarly, FIG. 6 shows the 353^(rd) nucleotide to the 371^(st)nucleotide of the SEQ No. 1 of JRA1 strain as an example of a“candidate” region for setting a primer and a probe for selectivelydetecting HEV, and the region corresponding thereto of known strains.The polynucleotide shown as the nucleotide sequences of the SEQ Nos. 1to 7 or the complementary strand of any one of the nucleotide sequencesof the SEQ Nos. 1 and 7 (specifically, the polynucleotide including thenucleotide sequence of the SEQ No. 6 or the complementary strand of thenucleotide sequence of the SEQ No. 6), for example, can be used as aprimer and a probe for selectively detecting HEV. On the other hand, theregion of the SEQ Nos. 1 and 7 which can be used as a primer and a probefor selectively detecting HEV is not limited thereto.

[0080] In a further embodiment of the present invention, apolynucleotide including, as a portion thereof, the polynucleotide ofthe SEQ Nos. 1 to 7 or a fragment of the polynucleotide of the SEQ Nos.1 to 7 is provided. The polynucleotide of the present embodiment may bea polynucleotide including a specific polynucleotide, which specificpolynucleotide is obtained as a result of bonding of at least one typeof a polynucleotide selected from the group consisting of: genes of apromoter, an enhancer, an upstream activation sequence, a silencer, anupstream repression sequence, an attenuator, poly(A) tail, nucleustransition signal, ISRE, a drug resistance factor, and a signal-peptidegene; gene of a membrane-penetration region; and gene of a markerprotein including luciferin, green fluorescent protein, phycocyanin andhorseradish peroxidase. Alternatively, the polynucleotide of the presentembodiment may be a polynucleotide including any other suitablenucleotide sequence.

(3) Polypeptide

[0081] In another embodiment of the present invention, a polypeptide asthe amino acid sequence disclosed at the SEQ No. 8 is provided. Theinventors of the present invention have demonstrated, by the clinicalstudy, that the aforementioned polypeptide of the present embodiment isa polypeptide produced at an early stage in a HEV-JRA1 patient and thatthe antibody specific to the polypeptide is an antibody produced at anearly stage in a HEV-JRA1 patient. Accordingly, the polypeptide and/orthe antibody of the present embodiment can be used as a marker forHEV-JRA1 detection. The polypeptide and the antibody as described abovecan be obtained by the known methods. A polypeptide obtained as a resultof modification such as deletion, substitution, addition of one or a fewpeptides, of a fragment of the aforementioned polypeptide, a polypeptideincluding the fragment, and an amino acid sequence disclosed at the SEQNo. 8, is also included within the scope of the present invention.

[0082] According to the present embodiment, if the polypeptide is asynthesized peptide, for example, and when the polypeptide is used as apolypeptide for antibody detection in which an antibody is detected as aresult of bonding of the antibody to the polypeptide, the polypeptide ofthe present embodiment may include the polypeptide shown as thesequential 15 to 50 amino acid residue contained in the SEQ No. 8. Ifthe polypeptide of the present embodiment is an expressed protein, theprotein may include the polypeptide shown as the sequential 150 to 250amino acid residue contained in the SEQ No. 8.

3. HEV Japan JSN-FH Strain (1) HEV Japan JSN-FH Strain

[0083] As described above, JSN-FH strain is a novel HEV strain isolatedfrom a patient of a fulminant hepatitis case. The method of medicaltreatment is completely different between fulminant hepatitis andordinary acute hepatitis. Accordingly, if the disease is diagnosed asfulminant hepatitis at an early stage, in other words, if the diagnosisas fulminant hepatitis can be made soon after the infection, thepossibility of survival increases. However, the amount of HEV virusexpression in a fulminant hepatitis patient is extremely small.Therefore, there were previously scant reports that HEV was successfullyrecovered from a fulminant hepatitis patient. Needless to say,determining the sequence over the whole length of HEV has been regardedvirtually impossible. However, the inventors of the present inventionhave succeeded in molecular cloning of HEV from a fulminant hepatitispatient and also in determining the approximate whole length (or theapproximate semi-whole length) of the genome of the HEV.

[0084] The genome of HEV recovered from a fulminant hepatitis patienthad a unique sequence, as a whole. In one of the clones obtained bysub-cloning, a new point mutation was found. The mutation produces apremature stop codon in an open reading frame (ORF2) coding nucleocapsidprotein and shortens the length of the translated product, from 660amino acids which would be the length if ORF2 of the normal hepatitis Evirus strain were to effect coding, to 211 amino acids. In short, the212^(th) codon of ORF2 was replaced with any one of the stop codons TAA,TAG and TGA.

[0085] For hepatitis B, it has been found that, when a patient has beeninfected with a variant (strain) in which the translated product codedby the pre-core/core region cannot reach the full size, the patient islikely to develop fulminant hepatitis.

[0086] The nucleotide sequence of JSN-FH strain and the nucleotidesequence of “Mexico” strain (M74506) are shown in FIGS. 7 to 12 in amanner that the former is compared with the latter. The nucleotidesequence of HEV JSN-FH strain and the nucleotide sequence of “Mexico”strain (M74506) are shown in a juxtaposed manner, such that thenucleotide sequence of JSN-FH strain is located upper and thecorresponding nucleotide sequence of “Mexico” strain (M74506) is locatedtherebelow. In this case, the rate of homology is 69.4% per 2631nucleotides.

[0087] Accordingly, as such a specific novel sequence as described aboveof JSN-FH strain has been revealed, JSN-FH strain, which has never beensubjected to detection and thus never been properly detected, can now bedetected in an easy and accurate manner. Further, it is expected thatthe strains which are genetically close to JSN-FH strain, which had notbeen detected by the conventional method, can also be detected by thepresent invention. If JSN-FH strain is detected in a patient, the resultindicates that the patient is likely to develop fulminant hepatitis.

(2) Polynucleotide

[0088] In a further embodiment of the present invention, apolynucleotide which is specific to JSN-FH strain and has a novelsequence is provided. The polynucleotide of the present embodiment maybe, for example, a polynucleotide shown as a nucleotide sequence of SEQNo. 11 containing 7234 nucleotides. Alternatively, the polynucleotidemay be a polynucleotide fragment, as a nucleotide sequence of any of theregions of the SEQ No. 11 nucleotide sequence. Specifically, thepolynucleotide may be a polynucleotide shown as the nucleotide sequenceof SEQ No. 22 containing 238 nucleotides. Or, the polynucleotide of thepresent embodiment may be a complementary strand of any one of thenucleotide sequences described above. Or, the polynucleotide of thepresent embodiment may be a polynucleotide fragment, as a nucleotidesequence which constitutes a portion of any one of the aforementionedpolynucleotide and the complementary strand thereof.

[0089] Further, as the polynucleotide for determining whether or not thestrain has a stop codon in ORF2, polynucleotides having the nucleotidesequences disclosed at the SEQ Nos. 9 and 10, and complementary strandsof the polynucleotides having the nucleotide sequences disclosed at theSEQ Nos. 9 and 10, and a polynucleotide fragment having a fragment ofany one of the aforementioned polynucleotides or the complementarystrands thereof, may be provided. A primer and a probe may be providedusing the polynucleotide described above. The nucleotide sequencedisclosed at the SEQ Nos. 9 and 10 each represents a nucleotide sequenceof a portion of ORF2 of JSN-FH strain. The nucleotide sequence disclosedat the SEQ No. 9 represents a nucleotide sequence which allowsspecifically detecting a strain not having a stop codon. The nucleotidesequence disclosed at the SEQ No. 10 represents a nucleotide sequencewhich allows specifically detecting a strain having a stop codon. Aprimer including a nucleotide sequence for amplifying a nucleotideportion including the aforementioned portion, also falls within thescope of the present invention. By detecting a nucleotide sequence whichdoes not allow production of the full-size product of translation inORF2 of the nucleic acid contained in the sample collected from theobject, and detecting, on the basis of the aforementioned detection,that the object has been infected with a virus strain having such a stopcodon in ORF2, it is possible to diagnose, at an early stage ofinfection, that the object or the patient has been infected withfulminant hepatitis virus.

[0090] One or a few nucleotides of each polynucleotide described abovemay be modified by, for example, deletion, substitution or addition.

[0091] In another embodiment of the present invention, a primer and aprobe each constituted of any one of the nucleotide sequences disclosedat the SEQ Nos. 11 and 22 or the complementary strand thereof or apolynucleotide fragment having a fragment of any one of the nucleotidesequences of the SEQ Nos. 11 and 22 and the complementary strandsthereof, are provided. The primer and probe may be used as a primer forvarious amplification for detecting HEV in the detection object (forexample, as a primer for PCR amplification or the like), or as a probeused in a “DNA chip”. In this case, the number of nucleotides containedin the polynucleotide of the present embodiment is preferably in a rangeof 10 to 30, inclusive. As previously mentioned, if the length of thepolynucleotide fragment is too long, it will be difficult to recognizethe difference between the fragments, and the difference could be onenucleotide. If the length of the polynucleotide is too short, it willgenerally be difficult to determine the nucleotide sequence ofpolynucleotide contained in the sample.

[0092] According to the present embodiment, polynucleotides of the SEQNos. 11, 22, 9 and 10 or a polynucleotide including, as a portionthereof, a fragment of any one of the polynucleotides of the SEQ Nos.11, 22, 9 and 10 is provided. The polynucleotide of the presentembodiment may be a polynucleotide including a specific polynucleotide,and this polynucleotide is obtained as a result of bonding of at leastone type of polynucleotide selected from the group consisting of: genesof a promoter, an enhancer, an upstream activation sequence, a silencer,an upstream repression sequence, an attenuator, poly(A) tail, nucleustransition signal, ISRE, a drug resistance factor, and a signal-peptidegene; gene of a membrane-penetration region; and gene of a markerprotein including luciferin, green fluorescent protein, phycocyaninand/or horseradish peroxidase. Alternatively, the polynucleotide of thepresent embodiment may be a polynucleotide including any other suitablenucleotide sequence.

(3) Polypeptide

[0093] Further, in yet another embodiment of the present invention,polypeptides as the amino acid sequences disclosed at the SEQ Nos. 12and 13 are provided. The amino acid sequence disclosed at the SEQ No. 12is an amino acid sequence corresponding to the region of ORF1 of thegenome sequence of JSN-FH strain. The amino acid sequence disclosed atthe SEQ No. 13 is an amino acid sequence corresponding to the region ofORF2 of the genome sequence of JSN-FH strain.

[0094] The polypeptide and/or the antibody of the present embodiment canbe used as a marker for JSN-FH detection. The polypeptide and theantibody as described above can be obtained by known methods. Apolypeptide obtained as a result of modification such as deletion,substitution, addition of one or a few peptides, of a fragment of theaforementioned polypeptide, a polypeptide including the fragment, and anamino acid sequence disclosed at the SEQ No. 12 or No. 13, is alsoincluded within the scope of the present invention.

[0095] According to the present embodiment, if the polypeptide is asynthesized peptide, for example, and when the polypeptide is used as apolypeptide for antibody detection in which an antibody is detected as aresult of bonding of the antibody to the polypeptide, the polypeptide ofthe present embodiment may include the polypeptide shown as thesequential 15 to 50 amino acid residue contained in the SEQ No. 12 orNo. 13. If the polypeptide of the present embodiment is an expressedprotein, the protein may include the polypeptide shown as the sequential150 to 250 amino acid residue contained in the SEQ No. 12 or No. 13.

[0096] ORF1, which is represented by the SEQ No. 12, is a region codingvarious enzyme proteins necessary for replication of virion or otherpurposes. Accordingly, in addition to the data of the primary structurei.e., the SEQ No. 12, the data of the secondary structure and/or thetertiary structure of the protein(s) may be further obtained by knownmethods, such as X-ray diffraction, so that drug design can be carriedout on the basis of the obtained data. Such drug design itself and amedicine obtained from the drug design are also included within thescope of the present invention.

[0097] An antibody specific to the shortened nucleocapsid protein,derived from ORF2 represented by the SEQ No. 13, may be produced by theknown methods. By utilizing an antigen-antibody reaction in which theantibody as described above is used, HEV infection can be easilydiagnosed, using a sample collected from the object.

[0098] An antibody for recognizing the antibody specific to thenucleocapside protein may be produced by a known method. By utilizingsuch an antibody, HEV infection can be easily diagnosed, using a samplecollected from the object.

4. Comparison of the Novel HEV Strain with the Conventional HEV Strain(1) Comparison of the Novel HEV Strain with the Conventional HEV Strain

[0099]FIG. 13 shows the results of comparison in which HEV Burma B1strain (M73218), HEV Mexico strain (M74506), HEV USA US-1 strain(AF060669), HEV Japan JRA1 (AP003430), Genotype 4 and HEV Japan JSN-FHare compared with each other, with regards to the location of ORF ineach of the genome sequence thereof. The number in parenthesis addedafter the name of each strain is the NCBI accession number. Note that,in the present invention, “HEV” of each strain name may omitted (forexample, HEV USA US-1 strain may read “USA US-1 strain”).

[0100] The Roman numerals shown in parenthesis, next to each strainname, represent the genotype to which each strain belongs. As shown inFIG. 13, a termination codon TGA is present in OFR2 of JSN-FH strain.

[0101]FIG. 14 shows a phylogenetic tree produced (according to theneighbor-joining method) on the basis of the 326nt region of ORF1, whichrepresents genealogy of the strains of 7 types endemic to Japan,including the novel strains of 5 types of the present invention, and theHEV strains found in the countries other than Japan. As shown in FIG.14, JMM-Sai was classified into type I. JKN-Sap, JHA-Sap and JMY-Hawwere each classified into type III. JSY-Sap, JKK-Sap and JAK-Sai wereeach classified into type IV.

[0102] In FIGS. 15 to 18, the information of the nucleotide sequence ofthe ORF1 region of the following examples is shown, in a juxtaposedmanner, for comparison. The examples include: the strains endemic toJapan of 5 types, as one embodiment of the present invention, i.e.,{Japan JRA1 strain (SEQ No. 15), JKN-Sap strain (SEQ No. 16), JMY-Hawstrain (SEQ No. 17), JKK-Sap strain (SEQ No. 21) and JAK-Sai strain (SEQNo. 20)}; the strain derived from a fulminant hepatitis patient (JSN-FHstrain, SEQ No. 22); and the known foreign strains i.e., {USA US-1(AF060669, SEQ No. 18), SWINE HEV (AF082843, SEQ No. 19), China type4(AJ272108, SEQ No. 23), Burma B1 (M73218, SEQ No. 24), China Uigh(D11093, SEQ No. 25), China Hebei (M94177, SEQ No. 26), China Xinjiang(D11092, SEQ No. 27), Nepali (AF051830, SEQ No. 28), India FH strain(X98292, SEQ No. 29), Pakistan SAR55 (M80581, SEQ No. 30), and Mexico(M74506, SEQ No. 31)}.

[0103] In FIGS. 15 to 18, the strain names, the NCBI accession No. shownin parenthesis next to the strain names, and the information ofnucleotide sequence next to the NCBI accession No. are shown in theaforementioned order. The numbers shown at both ends of the sequenceeach represent the number of nucleotide, counted from thetranscript-initiation site whose number is “1”. JRA 1 strain, shown asthe uppermost sequence in FIGS. 15-18, is regarded as the reference.When the type of the nucleotide at a specific position of another straincoincides with the type of the nucleotide of JRA1 strain at thecorresponding position, the nucleotide of the former is indicated by thesymbol “.”. When the type of the nucleotide at a specific position ofanother strain differs from the type of the nucleotide of JRA1 strain atthe corresponding position, the type of the nucleotide of the former isidentified as it is. At the lowermost sequence in FIGS. 15 to 18, thedegree of conservation of sequence at the plurality of nucleotidesequences shown in the juxtaposed manner is indicated. Specifically, thesymbol “*” at the lowermost sequence indicates that the type of thenucleotide at the specific position is the same throughout the pluralityof strains. On the other hand, the symbol “.” at the lowermost sequenceindicates that type of the nucleotide at the specific position of thesequence is different between JRA1 strain and non-JRA1 strains, in atleast one strain of the latter.

[0104] All of the novel strains and the nucleotide sequences thereofdescribed above are included within the scope of the present invention.

(2) Polynucleotide

[0105] According to a further embodiment of the present invention,polynucleotides which are specific to the strains JKN-Sap, JMY-Haw,JKK-Sap and JAK-Sai, respectively, and each have a novel sequence, areprovided. The nucleotide sequence of the present embodiment may be, forexample, a polynucleotide shown as a nucleotide sequence of any of theSEQ No. 44, the SEQ No. 45, the SEQ No. 46 and the SEQ No. 47, whichnucleotide sequences represent the genome sequence of JKN-Sap, JMY-Haw,JKK-Sap and JAK-Sai, respectively. Alternatively, the polynucleotide maybe the complementary strand of each of the nucleotide sequencesdescribed above. Yet alternatively, the polynucleotide may be apolynucleotide fragment, which constitutes a portion of any one of theaforementioned polynucleotides and the polynucleotides as thecomplementary strands thereof.

[0106] The polynucleotide of the present embodiment may be apolynucleotide fragment shown as the nucleotide sequence of any of theregions of the polynucleotide. The polynucleotide of the presentinvention may be a polynucleotide shown as a nucleotide sequence of anyof the SEQ No. 16, the SEQ No. 17, the SEQ No. 20 and the SEQ No. 21coding the ORF1 region. Or, the polynucleotide of the present embodimentmay be a complementary strand of any one of the nucleotide sequencesdescribed above. Or, the polynucleotide of the present embodiment may bea polynucleotide fragment, which constitutes a portion of any one of theaforementioned polynucleotides and the complementary strands thereof.

[0107] Further, a primer including a nucleotide sequence for amplifyingthe nucleotide portion, including the nucleotide sequences of the SEQNo. 16, the SEQ No. 17, the SEQ No. 20 and the SEQ No. 21, is includedwithin the scope of the present invention.

[0108] One or a few peptides of each polynucleotide described above maybe subjected to modification such as deletion, substitution andaddition.

[0109] In a further embodiment of the present invention, a primer and aprobe each constituted of any one of the nucleotide sequences of the SEQNo. 44, the SEQ No. 45, the SEQ No. 46 and the SEQ No. 47 or thecomplementary strands thereof or a polynucleotide fragment having afragment of any one of the nucleotide sequences of the SEQ Nos. 44 to 47and the complementary strands thereof, are provided. The primer andprobe may be used as a primer for various amplification for detectingHEV in the detection object (for example, as a primer for PCRamplification or the like), or as a probe used in a “DNA chip”. Aspreviously mentioned number of nucleotide contained in thepolynucleotide of the present embodiment is preferably in a range of 10to 30, inclusive. If the length of the polynucleotide fragment is toolong, it will be difficult to recognize the difference between thefragments, and the difference could be one nucleotide. If the length ofthe polynucleotide is too short, it will be difficult to determine thenucleotide sequence of polynucleotide contained in the sample.

[0110] Further, another embodiment of the present invention, apolynucleotide including, as a portion thereof, the polynucleotide ofany of the SEQ No. 44, the SEQ No. 45, the SEQ No. 46 and the SEQ No.47, as well as the SEQ No. 16, the SEQ No. 17, the SEQ No. 20 and theSEQ No. 21 or a polynucleotide having, as a portion thereof, a fragmentof these polynucleotides is provided. The polynucleotide of the presentembodiment may be a polynucleotide including a specific polynucleotide,obtained as a result of bonding of at least one type of polynucleotideselected from the group consisting of: genes of a promoter, an enhancer,an upstream activation sequence, a silencer, an upstream repressionsequence, an attenuator, poly(A) tail, nucleus transition signal, ISRE,a drug resistance factor, and a signal-peptide gene; gene of amembrane-penetration region; and gene of a marker protein includingluciferin, green fluorescent protein, phycocyanin and horse radishperoxidase. Alternatively, the polynucleotide of the present embodimentmay include any other suitable nucleotide sequence.

(3) Polypeptide

[0111] In another embodiment of the present invention, polypeptidesshown as the amino acid sequences coded by the polynucleotide sequencedisclosed at the SEQ No. 44, the SEQ No. 45, the SEQ No. 46 and the SEQNo. 47, as well as the SEQ No. 16, the SEQ No. 17, the SEQ No. 20 andthe SEQ No. 21, which are specific to the strains of JKN-Sap, JMY-Haw,JKK-Sap and JAK-Sai, respectively, are provided. Further, the presentembodiment provides polypeptides and the fragments thereof, and thepolypeptides are shown by the amino acid sequences of the SEQ No. 50,the SEQ No. 52, the SEQ No. 54 and the SEQ No. 56 representing the aminoacid sequences of the ORF1 region and the SEQ No. 51, the SEQ No. 53,the SEQ No. 55 and the SEQ No. 57 representing the amino acid sequencesof the ORF2 region, specific to the strains of JKN-Sap, JMY-Haw, JKK-Sapand JAK-Sai, respectively.

[0112] The polypeptide derived from the amino acid sequence coded by theORF1 region can be utilized in carrying out drug design.

[0113] The polypeptide derived from the amino acid sequence coded by theORF2 region can be used for producing an antibody for detecting therespective strains. Alternatively, the polypeptide derived from theamino acid sequence coded by the ORF2 region can, by itself, be used asan antibody for detection of diagnostic purpose. Or, vaccine may beproduced by utilizing this polypeptide.

[0114] According to the present embodiment, if the polypeptide is asynthesized peptide, for example, and when the polypeptide is used as apolypeptide for antibody detection in which an antibody is detected as aresult of bonding of the antibody to the polypeptide, the polypeptide ofthe present embodiment may include the amino acid sequence shown by theORF2 region of the nucleotide sequence derived from the respective novelstrains, e.g., the polypeptide shown as the sequential 15 to 50 aminoacid residues contained in the SEQ No. 51, the SEQ No. 53, No. 55 or theSEQ No. 57. If the polypeptide of the present embodiment is an expressedprotein, the protein may include the polypeptide shown as the sequential150 to 250 amino acid residue contained in the SEQ No. 51, the SEQ No.53, No. 55 or the SEQ No. 57.

[0115] The polypeptide and/or the antibody described above can also beused as a marker for detecting HEV JKN-Sap, JMY-Haw, JKK-Sap andJAK-Sai, respectively. The polypeptide and the antibody as describedabove can be obtained by the known methods. A polypeptide obtained as aresult of modification such as deletion, substitution, addition of oneor a few peptides, of a fragment of the aforementioned polypeptide, apolypeptide including the fragment, and an amino acid sequence disclosedat the SEQ Nos. 50 to 57, is also included within the scope of thepresent invention.

[0116] According to the present embodiment, if the polypeptide is asynthesized peptide, for example, and when the polypeptide is used as apolypeptide for antibody detection in which an antibody is detected as aresult of bonding of the antibody to the polypeptide, the presentpolypeptide may include the polypeptide shown as the sequential 15 to 50amino acid residues contained in the SEQ No. 8. If the polypeptide ofthe present embodiment is an expressed protein, the protein may includethe polypeptide shown as the sequential 150 to 250 amino acid residuescontained in the SEQ No. 8.

5. Primer and Probe for Comprehensively Detecting HEV

[0117] As a result of the aforementioned discovery of the novel HEVstrains and the determination of the nucleotide sequence thereof, aprimer which can amplify the HEV genome of a variety of types (includingunknown types) all at a time, that is, a universal primer (i.e., aprimer for comprehensive HEV detection) can be provided. Further, aprobe which can detect HEV of a variety of types (including unknowntypes) all at a time (i.e., a probe for comprehensive HEV detection) canbe provided. Such a universal primer will be described hereinafter.

[0118] In FIGS. 15 to 18, the nucleotide sequences of ORF1 of therepresentative HEV strains, each of which belongs to Group I, II, III orIV, are listed. In the tables of FIGS. 15 to 18, the symbol shown insidethe parenthesis next to the strain name is the NCBI accession No. Thenumbers shown at both ends of the sequence each represent the number ofthe nucleotide, counted from the transcript-initiation site whose numberis “1”.

[0119] The term “universal primer” or “universal probe” represents apolynucleotide fragment containing nucleic acid including a nucleotidesequence which allows comprehensive detection of HEV including unknownstrains. For example, the nucleotide sequence of such a universal primercan be selected from the sequences shown in FIGS. 15 to 18. The sequenceis, for example, preferably a highly conserved region.

[0120] The term “highly-conserved region” used in the present inventionindicates a region which exhibits high homology, e.g., 90% or more,preferably 95% or more, and most preferably 100% of homology between thenucleotide sequence of HEV-JRA1 strain and the corresponding nucleotidesequence of a known strain.

[0121] FIGS. 15 to 18 show an example in which a portion of theinformation of nucleotide sequence of JSN-FH strain is compared with theinformation of nucleotide sequence of known strains at the correspondingsite. By comparing the nucleotide sequence of JSN-FH strain with thenucleotide sequence of the known strains in such a manner, it ispossible to clearly identify a highly-conserved region useful forsetting a primer/probe for comprehensively detecting HEV and ahighly-mutated region for selectively detecting each genotype of HEV.

[0122] FIGS. 15 to 18 show an example of a “candidate” region forsetting a primer and a probe for comprehensively detecting HEV.Preferable examples of the highly conserved region include: the regionindicated by “(1)” in FIG. 15, i.e., the range from the 19^(th)(nucleotide) to the 37^(th) (nucleotide) of the SEQ No. 15 of HEV-JRA1strain and the corresponding region of the known strains; the regionindicated by “(4)” in FIG. 16, i.e., the range from the 111^(th) to the127^(th) of the SEQ No. 15 of HEV-JRA1 strain and the correspondingregion of the known strains; the region indicated by “(5)” in FIG. 17,i.e., the range from the 174^(th) to the 181^(st) of the SEQ No. 15 ofHEV-JRA1 strain and the corresponding region of the known strains; andthe region indicated by “(6)” in FIG. 17, i.e., the range from the213^(th) to the 220^(th) of the SEQ No. 15 of HEV-JRA1 strain and thecorresponding region of the known strains.

[0123] Regarding the primer for comprehensively detecting HEV, use of apolynucleotide of preferably 6 to 100 nucleotides, more preferably 15 to25 nucleotides having a sequence as included in the (1) region of FIG.15, as a sense primer, is preferable. Use of a polynucleotide ofpreferably 6 to 100 nucleotides, more preferably 15 to 25 nucleotideshaving a sequence as included in the (4), (5) and/or (6) regions of FIG.15, as a sense primer, together with the aforementioned sense primer, ismore preferable.

[0124] The region indicated by “(7)” in FIGS. 15 and 16, i.e., the rangefrom the 48^(th) to the 100^(th) of the SEQ No. 15 of HEV-JRA1 strainand the corresponding region of the known strains can also be used asthe primer groups for comprehensively detecting HEV. In this case, thesequence extending over the entire length of the (7) region is notnecessary and any suitable sequence of preferably 6 to 25 nucleotides,more preferably 15 to 22 nucleotides selected from the (7) region can beused. Preferable examples of the primer for comprehensively detectingHEV include:

[0125] 5′-gcagaccacrtatgtgktcg-3′ (SEQ No. 32);

[0126] 5′-ccacrtatgtggtcgaygcc-3′ (SEQ No. 33);

[0127] 5′-acmarctgscgrggytgcat-3′ (SEQ No. 34);

[0128] 5′-cgytgratwggrtgrttcca-3′ (SEQ No. 35);

[0129] 5′-tgktcgaygccatggaggc-3′ (SEQ No. 36);

[0130] 5′-tgktcgaygccatggaggc-3′ (SEQ No. 37);

[0131] 5′-aygccatggaggcccaycag-3′ (SEQ No. 38);

[0132] 5′-ckracyaccacagcattcgc-3′ (SEQ No. 39); and

[0133] 5′-ggcckracyaccacagcatt-3′ (SEQ No. 40).

[0134] In the present specification, “a” or “A” represents adenine, “c”or “C” represents cytosine, “g” or “G” represents guanine, “t” or “T”represents thymine, “r” or “R” represents G or A. “y” or “Y” representsT or U or U. “w” or “W” represents A or T or U.

[0135] It is more preferable that the aforementioned primer groups forcomprehensively detecting HEV is used, for example, for two-stagedanalysis as follows. In one example, the SEQ No. 32 and the SEQ No. 33described above are used as sense primers and the SEQ No. 34 and the SEQNo. 35 described above are used as antisense primers, for the firstamplification. Then, the SEQ No. 36, the SEQ No. 37 and the SEQ No. 38described above are used as sense primers and the SEQ No. 39 and SEQ No.40 described above are used as antisense primers, for the secondamplification. As a result, polynucleotide fragments derived fromunknown HEV variant strains of a variety of types can be obtained. Theproducts obtained as a result of amplification may further be analyzedby known methods such as electrophoresis. The polynucleotide fragmentwhich has been analyzed may then be classified into genotypes.

[0136] When the aforementioned sequences are used as probes, apolynucleotide of preferably 6 to 100 nucleotides, more preferably 12 to25 nucleotides having a sequence including the sequences contained inthe (1) region of FIG. 15 is preferably used as the probe forcomprehensively detecting HEV. A polynucleotide of preferably 6 to 100nucleotides, more preferably 12 to 25 nucleotides having a sequenceincluding the sequences contained in the (4), (5) and/or (6) regions ofFIG. 15 is more preferably used as the probe for this purpose.

[0137] It should be noted that the primer for comprehensively detectingHEV of the present invention is not restricted to the above-describedpreferable examples thereof.

6. Nucleotide Sequence for Genotype Identification

[0138] A primer and probe for comprehensively detecting HEV can beobtained by selecting the sequence of the highly conserved region asdescribed above, and comprehensive virus detection is possible by usingthe obtained primer and probe. On the other hand, a primer and probe forselectively detecting HEV can be obtained by selecting the sequence ofthe highly mutated region. Selective detection and/or identification ofvirus can be possible by using such a highly mutated sequence.

[0139] The term “highly-mutated region” used in the presentspecification indicates a region which is a nucleotide sequence specificto HEV-JRA1 strain and exhibits relatively low homology, e.g., 80% orless, preferably 75% or less, and most preferably 70% or less ofhomology between the nucleotide sequence of HEV-JRA1 strain and thecorresponding nucleotide sequence of known strains.

[0140]FIGS. 15, 16, 17 and 18 show an example of a “candidate” regionfor setting a primer and a probe for selectively detecting HEV.Preferable examples of the highly mutated region include: the regionindicated by “(2)” in FIG. 15, i.e., the range from the 52^(nd)(nucleotide) to the 69^(th) (nucleotide) of the SEQ No. 15 of HEV-JRA1strain and the corresponding region of the known strains; and the regionindicated by “(3)” in FIG. 16, i.e., the range from the 77^(th) to the95^(th) of the SEQ No. 15 of HEV-JRA1 strain and the correspondingregion of the known strains.

[0141] The (2) region of FIG. 15 is a region where the nucleotidesequence changes according to the genotype thereof. The (2) region ofFIG. 15 has been demarcated to three portions according to thegenotypes. Specifically, the strain included in the portion having thesymbol “III” attached thereto in FIG. 15 belongs to genotype III. Thestrain included in the portion having the symbol “IV” attached theretoin FIG. 15 belongs to genotype IV. The portion having the symbol “I, II”attached thereto in FIG. 15 includes genotypes I or II. The (3) regionof FIG. 16 can be understood in a manner similar to the (2) region ofFIG. 15. In short, the HEV to be analyzed can be classified into therespective genotypes, by utilizing the difference in type of nucleotideat a specific position of the sequence between the respective genotypes.

[0142] When the aforementioned sequences are used as probes, apolynucleotide of preferably 6 to 100 nucleotides, more preferably 12 to25 nucleotides having a sequence including the sequences contained inthe (2) region of FIG. 15 is preferably used as the probe forselectively detecting HEV. A polynucleotide of preferably 6 to 100nucleotides, more preferably 12 to 25 nucleotides having a sequenceincluding the sequence(s) contained in the (3) region of FIG. 16 is morepreferably used as the probe for this purpose.

[0143] When the aforementioned sequences are used as primers, apolynucleotide of preferably 6 to 100 nucleotides, more preferably 12 to25 nucleotides having a sequence including the sequences contained inthe (2) region of FIG. 15 is preferably used as a primer for selectivelydetecting HEV. A polynucleotide of preferably 6 to 100 nucleotides, morepreferably 12 to 25 nucleotides having a sequence including the sequencecontained in the (3) region of FIG. 16 is more preferably used as theprobe for this purpose. Or, a primer which is capable of amplifyingpolynucleotide including at least the (2) region of FIG. 15 and/or the(3) region of FIG. 16 may be selected.

5. Method of Detecting HEV Virus

[0144] In a further embodiment of the present invention, a method ofdetecting HEV virus in a sample is provided.

[0145] The term “sample” used in the present embodiment represents; abiosample including blood, serum, lymph, tissues, and excrement such asfeces, urine or the like collected from a biont as the object; auntreated sample as an environmental sample e.g., water and soilcollected from the environment including rivers, sewage and the like;and a sample obtained by subjecting the aforementioned biosample or theenvironment sample to any necessary preparatory treatment such ashomogenation, extraction or the like. Such a preparatory treatment willbe easily selected by one skilled in the art, in accordance with thebiosample or the environmental sample used as the object.

[0146] According to the present embodiment, the method of detecting HEVvirus can be carried out, by using the primer described above, accordingto the known amplification method such as the polymerase chain reaction(which reaction is generally called as “PCR” and thus will be referredto as “PCR” hereinafter). Typical examples of PCR includes reversetranscription PCR, reverse transcription nested PCR, or modificationthereof such as reverse PCR, 5′ RACE and 3′ RACE.

[0147] The detection method as described above can be conducted, forexample, as follows. First, a desired primer is mixed with a samplecontaining hepatitis E virus genome. A PCR reaction is carried out underan appropriate PCR condition in which, for example, the temperature ischanged such that the initial 95° C. lasted for 4 minutes is followed by30 cycles of {95° C. for 30 seconds, 55° C. for 30 seconds, 72° C. for45 seconds} and the final 72° C. for 7 minutes. Thereafter, a genomefragment derived from hepatitis E virus can be detected by analyzing theproduct by means of electrophoresis, DNA chip or the like. As a result,the hepatitis E virus can be detected. For example, in the case in whichthe product is analyzed by electrophoresis, a genome fragment derivedfrom hepatitis E virus can be detected by determining presence/absenceof a band derived from HEV genome therein.

[0148] In another embodiment of the present invention, the method ofdetecting HEV virus can be carried out, by using the probe describedabove, according to a detection method in which the known hybridizationmethod is utilized. In this case, the probe can be labeled with adesired marker substance.

[0149] In short, virus detection in the comprehensive manner is possibleby using the aforementioned primer and probe for comprehensivelydetecting HEV. Alternatively, virus detection in the selective manner ispossible by using the aforementioned primer and probe for selectivelydetecting HEV.

[0150] For example, by designing a detection system in which a highlyconserved region is utilized, the precision of diagnosis of HEVinfection can be enhanced. On the other hand, a system for detectinggenotype specificity in which system a highly mutated region is utilizedcan make significant contribution to determination of the infectionroute and epidemiological study. The system for detecting genotypespecificity can also be used for a virus-check test with respect toblood to be used for blood transfusion and a virus-check test of asample derived from the environment.

[0151] According to the present embodiment, virus detection as describedabove can be achieved not only at the aforementioned nucleic acid levelbut also at the level of amino acid. For example, the amino acidsequence shown as the SEQ No. 8 and the like can be used as a markerwhich indicates the presence of HEV, as is the case with theaforementioned polynucleotide. Such an amino acid sequence can be used,for example, for comprehensively diagnosing infection of the virus in anorganism including human and for specifically diagnosing the genotype ofthe virus. Similarly, any of the aforementioned amino acid sequences canbe used for the purpose described above.

[0152] The gene and polynucleotide derived from HEV-JRA1 according tothe present invention described above is a novel substance. The methodof detecting HEV by using the polynucleotide or polypeptide and antibodyproduced from the polynucleotide excels the prior art, in usefulness oradvantage thereof in detecting virus genome, virus antibody and the likein a sample. The advantage of the present invention will be described indetail hereinafter by examples.

[0153] In order to improve the HEV detection method and the diagnosistechnique of HEV infection, it is preferable that the nucleotidesequence information of the gene of such a novel strain as describedabove is reflected on the detection and diagnosis systems.

8. Chip for Detecting Nucleotide Sequence

[0154] According to one embodiment of the present invention, a chip fordetecting nucleotide sequence, which chip includes the aforementionedpolynucleotide, is provided. Examples of the nucleotidesequence-detection chip of the present embodiment include DNA chip forfluorescent detection, DNA chip of electric current-detection type andthe like. However, the nucleotide sequence-detection chip of the presentembodiment is not restricted to these examples. The detection method issimplified and made effective, by detecting virus by employing a chipfor detecting nucleotide sequence in which chip the aforementionedpolynucleotide or a complementary strand thereof is arranged as a probe.The chip for detecting nucleotide sequence can be produced according tothe following procedure.

(a) Production of a Chip for Detecting Nucleotide Sequence, to be UsedFluorescent Detection

[0155] A polynucleotide according to the present invention or apolynucleotide having a sequence as a portion of the polynucleotide or apolynucleotide having a sequence complementary to any one of thesequences of these polynucleotides, are fixed on a substrate. As thesubstrate, any substrate of the conventional type e.g., a glasssubstrate or a silicon substrate can be used. Regarding the fixingmeans, any suitable means known to one skilled in the art, including ameans utilizing a spotter and a means utilizing the generalsemiconductor technique, can be used.

(b) Production of a Nucleotide Sequence Detection Chip of ElectricCurrent Detection Type

[0156] A polynucleotide according to the present invention or apolynucleotide having a sequence as a portion of the polynucleotide or apolynucleotide having a sequence complementary to any one of thesequences of these polynucleotides, are fixed on a substrate, e.g., anelectrode substrate, by means of covalent bond, ionic bond, physicaladsorption or chemical adsorption. Examples of the DNA chip of electriccurrent detection type include a gene detection device disclosed by JP-BNo. 2573443 (issued on Oct. 24, 1996) and the like. However, the chipfor detecting nucleotide sequence, of electric current detection type,of the present invention is not restricted to these examples. JP-B No.2573443 is herein incorporated to the present specification byreference.

[0157] According to the present embodiment, detection of virus can becarried out easily and effectively, by detecting virus by using a probeand a chip for detecting gene sequence including the polynucleotides asdescribed above.

9. Protein Chip

[0158] In one embodiment of the present invention, a protein chip whichallows easy implementation of the detection method described above isprovided. In the protein chip, an antibody which recognizes theaforementioned polypeptide is arranged as a probe. By using this proteinchip, HEV in a sample can be detected in a simple, easy and efficientmanner. Examples of the protein chip include a protein chip forfluorescent detection (which is generally called as “fluorescentcolorant-type protein chip”), a protein chip of electric currentdetection type (which is generally called as “electric potential-typeprotein chip”) and the like. However, the protein chip of the presentembodiment is not restricted to these examples. Examples of theproduction procedure of the protein chip of the present embodiment willbe described below.

(a) Production of a Protein Chip for Fluorescent Detection

[0159] A monoclonal antibody of the aforementioned polypeptide isproduced in advance. The obtained monoclonal antibody is fixed on asubstrate. As the substrate, any substrate of the conventional typee.g., a glass substrate or a silicon substrate can be used. The fixingmeans may be selected from any suitable means known to one skilled inthe art, such as a means utilizing a spotter and a means utilizing thegeneral semiconductor technique. A fluorescent substance, a radioactiveisotope, a colorant or the like may be used for labeling for detection.

(b) Production of a Protein Chip of Electric Current Detection Type

[0160] A monoclonal antibody of the aforementioned polypeptide isproduced in advance. The obtained monoclonal antibody is fixed on asubstrate of a type generally used for the conventional electric currentdetection-type DNA chip, whereby a protein chip of electric currentdetection type of the present embodiment is produced.

[0161] According to the present embodiment, detection of a virus can becarried out easily and efficiently, by detecting virus by using aprotein chip including the aforementioned antibody.

[0162] Alternatively, the aforementioned polypeptide, in stead of theantibody, may be fixed on a substrate, for producing a chip, so thatthis chip is used for detecting an antibody specific to the polypeptide.

10. Diagnosis System

[0163] By using the novel HEV strain, the polynucleotide and thepolypeptide as described above according to the present invention, it ispossible to diagnose: whether or not the object has been infected withHEV; and/or, if the object has been infected with HEV, to which genotypethe HEV belongs; and/or whether or not the object has been infected withfulminating HEV.

[0164] The diagnosing method described above includes: for example,collecting a sample from the object by a known method; optionallycarrying out purification of the sample and/or amplification of thenucleic acid; and obtaining a nucleic acid sample by purification.Thereafter, the targeted diagnosis can be carried out by using thepolypeptide of the present invention, through detecting presence/absenceof amplification of the targeted sequence or detecting presence/absenceof hybridization. Or, the targeted diagnosis can be done by employingthe aforementioned polypeptide of the present invention as a polypeptidefor detecting antibody and utilizing the antigen-antibody reaction.

11. Vaccine for Preventive Purpose

[0165] In one embodiment of the present invention, a vaccine for HEV isprovided. The vaccine can be prepared by using at least one type ofpolypeptide selected from the immunogenic polypeptides derived from HEVcontaining nucleic acid coded by (i.e., derived from) the aforementionednucleotide sequence of the novel HEV virus of the present invention. Forexample, polypeptide of the ORF2 region of any of the aforementionednovel strains may be used. Production of vaccine containing theimmunogenic polypeptide can be carried out by using any of the suitableknown methods.

12. Drug Design

[0166] The genetic information derived from the aforementioned novel HEVis useful for development and improvement of antiviral agents. Suchdevelopment and improvement of antiviral agents can be carried out, forexample, by following process, by using the known method of drugdesigning generally called “post-genome drug designing”.

[0167] (1) The tertiary structure of enzyme proteins of a plurality oftypes, coded by ORF1 of the HEV genome, is actually measured by X-raydiffraction and/or NMR analysis of the expressed proteins.Alternatively, the tertiary structure of the enzyme proteins may beobtained by simulation on a computer, only on the basis of theinformation of the amino acid sequence. The “candidate” domain which canbe the target of the drug (which domain will be referred to as “receptordomain” hereinafter), of the enzyme protein, is searched on theinformation obtained by the measurement or the simulation.

[0168] (2) With regards to a drug whose inhibitory action against theenzymic activity of HEV ORF1 protein has been confirmed, a compoundwhich has already been synthesized, although the inhibitory effectthereof against the enzymic activity of HEV ORF1 protein has not beenconfirmed yet, a compound which has not been synthesized yet but whosestructural formula has been known, and an imaginary compound having anovel structure (each of which drug or compound will be referred to as“ligand” hereinafter), the tertiary structures thereof are inputted intoa computer, respectively.

[0169] (3) By using the data inputted into a computer in theaforementioned process (2), whether or not the receptor domain(“candidate” region) determined in the aforementioned process (1) can bethree-dimensionally bound to any of the ligands of the aforementionedprocess (2) is determined through three-dimensional docking analysis. Aneffective combination of a ligand with the receptor domain is selectedon the basis of the aforementioned determination. Alternatively,improvement of the ligand molecule necessary for causing more effectivedocking is simulated by the computer.

[0170] (4) A ligand obtained by the aforementioned process (3) (i.e., aligand selected or improved by the process (3)) is likely to function asan effective antiviral agent which suppresses or inhibits proliferationof HEV.

[0171] HEV is a virus which includes a number of variants. Therefore, inorder to develop and/or improve an antiviral agent being equallyeffective to all of the variant strains (or as many strains as possible)of HEV, it is necessary to obtain the information of nucleotide sequenceof all the existing strains (or as many existing strains as possible) ofHEV. According to the aforementioned aspects of the present invention,an advantageous effect is achieved in obtaining such information ofnucleotide sequence.

[0172] Any of the ORF1 regions derived from the aforementioned novel HEVstrains may be utilized in the manner described above. A drug obtainedby the aforementioned method of designing drug is also included withinthe scope of the present invention.

13. Assay kit

[0173] In the present invention, the polynucleotide, polynucleotidefragment, polynucleotide probe, polynucleotide primer, polypeptide,antigen and antibody of any of the aforementioned embodiments may beprovided as a kit in an appropriate manner, in accordance with theapplication purpose. For example, in order to produce a chip fordetecting nucleotide sequence, a kit may be formed by combining thepolynucleotide/polynucleotide's with a substrate and/or various reagentsand/or a marker substance. Further, a kit may be formed by combining thepolynucleotide probe with a reaction container and/or salts for buffersolution and/or other necessary reagents. For example, a kit may beformed by combining the polynucleotide primer with a reaction containerand/or salts for buffer solution and/or other necessary reagents e.g.,polymerase and/or a substrate. Note that the kit provided according tothe present invention is not restricted to the aforementioned examplesor combinations, but kits of other types may be provided according tonecessity by combining the polynucleotide/polypeptide/antigen/antibodycomponents of the present invention with various substances. Theapplication purpose of the kit is not restricted to the aforementionedexamples, either, and a kit for any of the application purposes orobjects described above may flexibly be formed. Such a kit as describedabove is also included within the scope of the present invention.

[0174] Examples with regards to HEV genome detection according to thepresent invention will be described hereinafter. It should be noted thatthe following description is provided only for a demonstrational purposeand by no means restricts the scope of the present invention.

EXAMPLE 1 Detection of HEV Genome RNA by RT-PCR Method 1. Primer

[0175] In the RT-PCR of the present example, four types ofoligonucleotide primers respectively having following nucleotidesequences, selected from the nucleotide sequences derived from HEV-JRA1disclosed at the SEQ No. 1 or the SEQ No. 2 of the sequence list, wereused.

[0176] #HE5-1 (5′-TCGATGCCATGGAGGCCCA-3′) (sense primer, whichcorresponds to nt 19-37 of the sequence list 1) (The underlined portioncorresponds to the SEQ No. 2 of the sequence list)

[0177] #HE5-2 (5′-GCCYTKGCGAATGCTGTGG-3′) (sense primer, whichcorresponds to nt 105-123 of the sequence list 1) (Y=C or T; K=G or T)(The underlined portion corresponds to the SEQ No. 3 of the sequencelist)

[0178] #HE5-3 (5′-TCRAARCAGTARGTGCGGTC-3′) (antisense primer, whichcorresponds to nt 450-469 of the sequence list 1) (R=A or G) (Theunderlined portion corresponds to the SEQ No. 4 of the sequence list)

[0179] #HE5-4 (5′-CATAGCCTCSGCRACATCAG-3′) (antisense primer, whichcorresponds to nt 541-560 of the sequence list 1) (S=G or C; R=A or G)(The underlined portion corresponds to the SEQ No. 5 of the sequencelist)

2. Detection Method

[0180] First, nucleic acid was extracted from 50 μL of the serumcollected from the patient, by using SMITEST EX R & D (Genome ScienceLaboratories). #HE5-4 as an antisense primer was added to the extractednucleic acid. The nucleic acid was reacted with the added antisenseprimer at 37° C. for 30 minutes, under the presence of polymeraseMMLV-RT (Stratagene), whereby the synthesis of cDNA (i.e., the reactionof reverse transcription from RNA to DNA) was carried out.

[0181] Next, the cDNA synthesized as described above was subjected tonested PCR by using the aforementioned four types of primers and FastStart Taq DNA Polymerase (Roche Co., Ltd.). During the nested PCR, thetemperature was changed such that the initial 95° C. lasted for 4minutes was followed by 30 cycles of {95° C. for 30 seconds, 55° C. for30 seconds, 72° C. for 45 seconds} and the final 72° C. for 7 minutes.The product obtained as a result of the PCR reaction was subjected toelectrophoresis by using agarose gel. Presence/absence of a band derivedfrom HEV genome having length of 365 bp was checked.

3. Result and Discussion

[0182]FIG. 19 shows the result of detecting HEV genome RNA by theaforementioned method, in a serum sample successively collected from aJapanese acute hepatitis patient. The graph of FIG. 7 shows changes inthe values of liver function test which indicate the progress ofhepatitis. The abbreviations of the terms used in FIG. 7 are as follows.“AST” represents aspartic aminotransferase. “ALT” represents alanineaminotransferase. “Total bilirubin” represents the concentration ofbilirubin as a whole. The photograph of FIG. 7 shows the result ofelectrophoresis of the PCR product, derived from the serum collectedfrom the same patient at the timing corresponding to the graph (i.e., byRT-PCR: the reverse transcription polymerase chain reaction method). TheX-axis represents the days during which the patient was hospitalized.

[0183] In the case shown in FIG. 7, HEV RNA was continually detected inthe serum of the patient, from the initial stage of the disease,throughout the hospitalized period exceeding 27 days. This is anepoch-making discovery which denies the conventional knowledge, becauseit has conventionally been considered, as common sense, that HEV RNAappears in blood only during a very short period until AST, ALT andTotal bilirubin reach the peaks thereof (Purcell, R. H. In FieldsVirology, eds. Fields, B. N., Knipe, D. M., & Howley, P. M.Lippincott-Raven, Philadelphia, 1996, 3^(rd) Ed., Vol. 2, pp.2831-2843). The results shown in FIG. 7 indicate that the detectionsystem of HEV genome RNA, which can be constructed according to thepresent invention, detects HEV genome RNA with very high sensitivity andthat the clinical data obtained from the analysis using such a detectionsystem effectively and thus usefully deepens the academic understandingof HEV infection.

EXAMPLE 2 Isolation of the Novel HEV Strain

[0184] Tests were conducted for seven acute hepatitis E patients ofseven cases. Among the seven cases, the patients of five cases in whichJHA-Sap, JKK-Sap, JKN-Sap, JMY-Haw and JSY-Sap were isolated had livedin Hokkaido. The patients of two cases in which JAK-Sai and JMM-Sai wereisolated had lived in Saitama prefecture. Each patient developed thedisease in an isolated manner i.e., with no contact with other patientsregarding both time and place. Further, the case of each patient hadnothing to do with any local epidemic of the disease. In six of theseven cases, patients had not been abroad recently. Only the patientfrom whom JMY-Haw was isolated had been to Hawaii as a tourist one monthbefore developing the disease. The serum sample was collected from thepatient at the acute state, frozen at a temperature of −20° C. or belowand stored until the virological analysis was carried out.

[0185] The HEV sequence was determined, basically according to themethod proposed by Takahashi (Takahashi K, Iwata K, Watanabe N, et al.Virology 2001; 287:9-12), with some improvements added thereto. Thenucleic acid sample was extracted from 25 mL of serum by using acommercially available kit for nucleic acid extraction (SMITEST EX-R & D(Genome Science Laboratories)). The first strand cDNA was synthesized at37° C. for 30 minutes by using the reverse transcripase of Moloney mouseleukemia virus (produced by Stratagene Co., Ltd.). As the antisenseprimer, a mixture of HE5-4 (5′-CATAGCCTCSGCRACATCAG-3′; NT541-560) andHE5-5 (5′-CATYGCCTCSGCAACATCGG-3′; nt541-560, the positions of therespective nucleotides correspond to those of HEV-JRA1 strain) was used.Next, the obtained cDNA was subjected to the nested polymerase chainreaction (referred to as “PCR” hereinafter). For the first round PCR, amixture of Fast Start Taq DNA Polymerase (produced by Roche Co., Ltd.),an outer-side sense primer HE5-1 (5′-TCGATGCCATGGAGGCCCA-3′; nt 19-37),and an outer-side antisense primer HE5-4/HE5-5 (with regards to thesequences thereof, refer to the aforementioned description), was used.Subsequently, for the second round PCR, a mixture of an inner-side senseprimer HE5-2 (5′-GCCYTKGCGAATGCTGTGG-3′; nt 105-123), an inner-sideantisense primer HE5-3 (5′-TCRAARCAGTARGTGCGGTC-3′; nt 450-569) andHE5-6 (5′-TYAAAACAGTAGGTTCGATC-3′; nt 450-469) was used. In theaforementioned PCR, the temperature was changed such that the initial95° C. lasted for 4 minutes was followed by 30 cycles of {95° C. for 30seconds, 55° C. for 30 seconds, 72° C. for 45 seconds} and the final 72°C. for 7 minutes.

[0186] As a result, the 326-nt region was amplified from ORF1 of the HEVgenome. Next, the sequencing process was carried out by using “DyeTerminator Cycle Sequencing FS Ready Reaction Kit” (produced byPerkin-Elmer Applied Biosystems Co., Ltd.) and “373A DNA sequencer”(produced by Applied Biosystem Co., Ltd.).

[0187] The sequences obtained from the strains isolated (i.e., derived)from the Japanese patients were compared with the sequences of thestrains isolated from patients of various foreign nationalities. Acomputer software (GENETYX-MAC version 10.1 (Software Development Co.,Ltd.) was used for comparison.

[0188] The result of the comparison described above is shown in FIG. 14.When the 326-nt ORF1 sequences of the seven strains endemic to Japanwere compared with each other, the seven strains were classified intothree main groups. JMM-Sai sequence exhibited homology of 73.0% to 75.7%with respect to each of the other six isolated strains. JKN-Sap, JHA-Sapand JMY-Haw exhibited relatively high homology of 95.4% to 98.8% withrespect to the strains belonging to the same group, but exhibitedrelatively low homology of 73.0% to 79.1% with respect to the isolatedstrains belonging to other groups. JSY-Sap, JKK-Sap and JAK-Saiexhibited relatively high homology of 89.0% to 99.7% with respect toeach other, but exhibited relatively low homology of 74.8% to 78.8% withrespect to the other four strains. The entire-length genome of JRA1strain as the prototype had homology of less than 90% with respect tothese isolated strains.

EXAMPLE 3 Comprehensive Detection of HEV

[0189] First, blood was collected from a plurality of patients. Nucleicacid was extracted from 50 μL of the serum collected from each patient,by using SMITEST EX R & D (Genome Science Laboratories).5′-gcagaccacrtatgtgktcg-3′ (SEQ No. 32) and 5′-ccacrtatgtggtcgaygcc-3′(SEQ No. 33) as the sense primers, as well as 5′-acmarctgscgrggytgcat-3′(SEQ No. 34) and 5′-cgytgratwggrtgrttcca-3′ (SEQ No. 35) as theantisense primers were added to each of the extracted nucleic acid. Eachnucleic acid was reacted with the added sense primer and antisenseprimer at 37° C. for 30 minutes, under the presence of polymeraseOne-step RT-PCR (Stratagene), whereby the synthesis of cDNA (i.e., thereaction of reverse transcription from RNA to DNA) was carried out.

[0190] Next, each of the cDNA synthesized as described above wassubjected to nested PCR by using: Fast Start Taq DNA Polymerase (RocheCo., Ltd.); 5′-tgktcgaygccatggaggc-3′ (SEQ No. 36),5′-tgktcgaygccatggaggc-3′ (SEQ No. 37) and 5′-aygccatggaggcccaycag-3′(SEQ No. 38) as the sense primer; and 5′-ckracyaccacagcattcgc-3′ (SEQNo. 39) and 5′-ggcckracyaccacagcatt-3′ (SEQ No. 40) as the antisenseprimer. During the nested PCR, the temperature was changed such that theinitial 95° C. lasted for 4 minutes was followed by 30 cycles of {95° C.for 30 seconds, 55° C. for 30 seconds, 72° C. for 45 seconds} and thefinal 72° C. for 7 minutes. The PCR product obtained as a result of thePCR reaction was subjected to electrophoresis by using agarose gel.

[0191] As a result, amplified products were obtained by theaforementioned method of the present example, for 8 cases of the total37 cases. For the 8 cases in each of which a band was obtained as aresult of electrophoresis, the obtained bands are schematically shown inFIG. 22. Each band obtained for each sample was observed at differentpositions, as shown in FIG. 22. This result indicates that, in theabove-described 8 cases, the plural primers used therein acted, as somedifferent combinations of the primers, on the HEV genome in the sampleand effected amplification. In other words, the result indicates thatthe genotypes of HEV detected in the HEV-positive patients are differentfrom each other.

[0192] The amplification reaction was carried out for each of the 37samples of the non-A,B,C type acute hepatitis patients. The result ofthe amplification is summarized in FIG. 20, in a manner that the resultobtained by the conventional method is compared with the result obtainedby the method of the present example. The column “Blood collection date”of FIG. 20 represents the date when blood was collected from eachpatient. The alphabet letters right next to “Blood collection date”represent the initials of the patient. “Sample No.” represents theserial sample number used in the hospital. The column “Comparativeexample” of FIG. 20 indicates presence/absence of HEV detection whenamplification was effected by using the conventional primer. The column“new-PCR” indicates presence/absence of HEV detection by the method ofthe present example. In each column of “Comparative example” and“new-PCR”, “+” indicates that HEV was detected and “−” indicates thatHEV was not detected. As shown in FIG. 20, the method of the presentexample was capable of detecting the virus strains which theconventional primer failed to detect, although the same amplificationand electrophoresis processes were conducted in the two cases.

EXAMPLE 4 Follow-Up Check of a Patient

[0193] For a patient who developed acute hepatitis E, presence/absenceof the virus in blood of the patient was successively checked. As themeasuring method, the method according to the present invention i.e.,the method described in example 3 and the conventional method describedin example 3 were employed. The result is shown in FIG. 21. The leftmostcolumn of FIG. 21 represents the date when blood was collected. Thenumber right next to “Blood collection date” indicates the period (days)counted from the day when the patient was hospitalized. “Sample No.” ofFIG. 21 represents the serial sample number used in the hospital. Thecolumn “Comparative example” of FIG. 21 indicates presence/absence ofHEV detection when amplification was effected by using the conventionalprimer. The column “new-PCR” indicates presence/absence of HEV detectionby the method of the present example. In each column of “Comparativeexample” and “new-PCR”, “+” indicates that HEV was detected and “−”indicates that HEV was not detected.

[0194] From the result of FIG. 21, it is understood that the methodusing the primer of the present invention enables detection of virus,even when the virus in blood has been reduced to such a degree that theconventional method can no longer detect the virus.

EXAMPLE 5 Genotype Identification of HEV

[0195] Next, for each of the products obtained as a result ofamplification in example 3, the genotype thereof was identified by usinga probe-fixed plate as described below.

(1) Probe-Fixed Plate

[0196] A probe of 53 mer(5′-aaggctcctggcrtyactactgcyatwgagcaggcwgctctrgcwgcggccaa-3′), a probefor HEV-I, II (5′-ctcctggcatcactactgc-3′), a probe for HEV-III(5′-ctcctggcattactactgc-3′) and a prove for HEV-IV(5′-ctcctggcgtcactactg-3′) were solid-phase fixed, respectively, on awell of a commercial microtiter platewell.

(2) Genotype Identification by Hybridization Assay

[0197] Each of the products obtained as a result of amplification inexample 3 was added to the probe-fixed plate prepared in theaforementioned (1), whereby hybridization was effected. Thereafter,optical density (O. D.) of each well was measured.

[0198] The results are shown in FIGS. 23A to 23E. The graphs of FIG.23A, FIG. 23B, FIG. 23C, FIG. 23D and FIG. 23E show the result ofgenotype identification conducted for the HEV having differentgenotypes, i.e., JRA1 strain, JKN-Sap strain, JKK-Sap strain, JAK-Saistrain and JMM-Sai strain, respectively. In all of the graphs, theX-axis represents the HEV-I, II solid phase well, the HEV-III solidphase well, and the HEV-IV (54 mer primer) solid phase well, from leftto right in this order. In the case of genotype III, only the O. D. ofthe well in which the probe for HEV-III had been solid-phase fixed wasdistinctly high. In the case of genotype IV, only the O. D. of the wellin which the probe for HEV-IV had been solid-phase fixed was distinctlyhigh. In the case of genotype I, the well in which the probe for HEV-I,II had been solid-phase fixed exhibited relatively high O. D., ascompared with the other wells. On the basis of the indexes describedabove, the genotype of the virus in the serum of each patient wasidentified by using the corresponding probe. The result of the genotypeidentification was shown in the column “genotype” of FIG. 20. As isobvious from the result shown in FIG. 20, it has been demonstrated thatgenotype identification of HEV collected from a patient can be easilycarried out by using the probe according to the present invention.

[0199] The total contents of all the references cited in the presentspecification are incorporated in the present specification, byreference.

1 57 1 5138 DNA Hepatitis E virus JRA1 1 ggcagaccac gtatgtggtcgatgccatgg aggcccacca gttcattaag gctcctggca 60 ttactactgc catagagcaggctgctctgg ctgcggccaa ctccgccttg gcgaatgctg 120 tggtggttcg gccgtttttgtctcgcgtac aaaccgagat ccttattaat ttgatgcaac 180 cccggcagtt ggttttccgccctgaggtgc tttggaacca tcctattcag agggttatac 240 acaatgaatt agaacagtactgccgggccc gggccggtcg ttgcctggag attggggctc 300 atccaagatc tattaatgataaccccaatg ttttgcaccg gtgttttctc aggccggtcg 360 gtagggacgt ccagcgctggtattctgccc ccacccgcgg ccctgcagcc aactgccgcc 420 gctctgcatt gcgtggcctcccccctgtcg accgcactta ctgttttgat ggattttcca 480 gttgtgcttt cgccgcagagaccggcgtgg ccctttactc tctacatgac ctttggccag 540 ctgatgttgc ggaggctatggcccgccatg gaatgacacg tctttatgct gcactccacc 600 tccctcccga ggtgttgttaccacccggta cttaccacac aacctcgtat cttctgatcc 660 atgacggcaa ccgtgctgttgtgacttatg aaggtgatac tagtgcaggt tacaaccatg 720 acgtttccat acttcgtgcatggattcgca cgactaaaat agttggtgac catccgttgg 780 ttatagagcg tgtgcgggctattggttgtc attttgtgct gctgctcacc gcggcccctg 840 agccatcgcc catgccttacgtcccttacc cccgttccac ggaggtgtat gtccgatcta 900 tatttggccc tggtggctccccatccttgt ttccgtcagc ttgctctaca aaatctacct 960 tccatgctgt tccagttcacatatgggacc ggcttatgct ttttggtgcc accttggacg 1020 accaggcgtt ttgctgctcacggctcatga catacctccg tggcattagc tacaaagtca 1080 ctgtcggtgc gcttgttgctaatgaggggt ggaatgcctc tgaagatgcc ctcaccgcag 1140 taatcactgc agcctacttgaccatctgtc accagcgcta cctccgtacc caggcgatat 1200 ctaagggtat gcgccggttggaggttgagc acgcccagaa gtttattaca agactttaca 1260 gctggttatt tgagaagtctggtcgtgact acatccccgg ccgccaactt cagttctatg 1320 cccagtgccg gcggtggctatctgcgggct ttcacctaga ccccagagtg ctcgtctttg 1380 atgagtcagt gccctgccgctgtaggactt tcttaaagaa ggttgcgggt aaattctgtt 1440 gcttcatgcg gtggttagggcaggagtgta cttgtttctt agaaccagct gagggcttag 1500 ttggcgatca aggccatgataatgaggctt atgagggttc tgaggttgac caggccgagc 1560 ctgtacacct tgatgtgtcggggacctatg ctgtccacgg gcaccagctt gaggccctct 1620 acagggcact caacattccacacgatattg ctgctcgagc tgcccgatta acggctactg 1680 ttgagctcgc tgcaggccccgaccgtctgg agtgccgcac cgtgctcggg aacaagactt 1740 tccggacgac ggtgactgatggcgcccatc tagaagcgaa cggccctgag caatatgttc 1800 tgtcgttcga tgcctcccgccagtctatgg gggccgggtc ccatagcctc acttacgagc 1860 ttacacccgc cggcttgcaggttaagatct catctaatgg cctagactgc actgccgtat 1920 tcccccctgg tggcgcccctagcgcgccgc cgggggaggt ggcggctttt tgcagcgccc 1980 tctacaggta taacagattcacccagcggc attcgctgac cggcggtttg tggctacatc 2040 ccgaggggtt gctaggcgttttcccccctt tttcccctgg gcacatttgg gagtctgcca 2100 accccttctg cggtgagggtaccttgtata ctcgcacctg gtctacatct ggtttttcta 2160 gtgacttttc ccctcctgaggcggccgccc ctgcaccggc tgccgcccca gggtcgtcct 2220 cccccactcc accagtcagtgatatttggg tgttaccacc gctttcagag gagccccagg 2280 tgggtgcgcc gcctgcacctcccacccccg agcctgctcg gctgccctgc cccactaaac 2340 ctaacacccc cgtgcgtaagccaacggcac cgccgccttc tcgcacccgc cgccttcttt 2400 acacctatcc tgatggtgctaaggtgtatg cggggtcact gtttgagtca gattgtgatt 2460 ggctggtgaa tgcctctaacccgggccatc gtcctggggg tggcctctgt cacgcctttt 2520 accaacgttt tcccgaggcgttctatccaa ctgaatttat tatgcgtgag ggtcttgcag 2580 catacacctt gaccccgcgccctattatcc atgcagtggc ccccgactat agggttgagc 2640 agaatccaaa gaggcttgaggcagcgtacc gagaaacttg ctcccgccgc ggcaccgctg 2700 cctatccact tcttggctcaggtatatacc aggtccctgc tggtcttagt tttgatgcct 2760 gggagcgtaa ccatcgccctggcgatgagc tttacctgac tgaacccgct gcagcctggt 2820 ttgaagctaa taagccaacgcagccagcac ttacgataac ggaagataca gctcgcacgg 2880 ccaacctagc attagagatcgatgctgcca cagacgttgg ccgtgcttgt gccggctgca 2940 ctattagccc cgggattgtgcattatcagt tcactgccgg ggtcccaggc tcaggcaaat 3000 caaggtccat acagcagggggatgtcgatg ttgtggttgt ccccacccgg gaacttcgca 3060 atagctggcg ccgtcggggctttgcggcct ttacacccca cacggcggcc cgtgttacta 3120 taggccgccg tgttgttattgacgaggccc catcccttcc accgcacttg ttgctgttac 3180 acatgcagcg ggcctcctcagtccatctcc tcggtgaccc aaatcagatc cctgccatcg 3240 acttcgagca tgccggcctggtccccgcaa ttcgccctga gcttgcacca acgagctggt 3300 ggcatgttac gcatcgctgtccggccgatg tatgtgagct catacgcgga gcctacccta 3360 aaatccagac cacgagccgtgtgctacggt ctctgttctg gaatgagccg gctattggcc 3420 agaagttggt cttcacgcaggccgctaaag ctgccaaccc tggtgcaatt acggtccatg 3480 aagcccaggg tgctaccttcacagagacca caattatagc cacggctgat gccaggggtc 3540 ttattcagtc atcccgggcccatgctatag ttgcacttac ccgccacaca gagaagtgcg 3600 ttattttgga tgcccctggtttgttgcgcg aggtcggcat atcagatgta attgttaaca 3660 actttttcct tgctggcggagaggtgggcc atcaccgccc ctctgtgata cctcgtggca 3720 atcctgaccg gaaccttgacaccctacagg ccttcccgcc atcctgccaa attagtgctt 3780 accatcagtt ggctgaggagttaggccatc gcccggctcc tgttgctgcc gttttgcccc 3840 cctgccccga gctcgagcagggcttattgt atatgccaca ggagcttaca gtgtccgata 3900 gtgtgttggt ttttgagctcactgacatag tccattgccg catggctgcc ccaagtcagc 3960 ggaaggccgt cctctcaacacttgtgggga ggtatggccg caagacgaaa ttgtatgagg 4020 cagcccattc agatgttcgagagtctctag ctaggttcat tcccactatc ggacctgtcc 4080 aggccaccac gtgtgagttatatgaactgg ttgaggccat ggtggaaaag ggccaggacg 4140 gctctgccgt cctggagcttgatctatgta atcgtgatgt ttcgcgcatt acattctttc 4200 agaaagactg taataagtttacaactggtg agaccattgc ccatggtaag gttggccagg 4260 gcatatcggc ctggagtaagaccttttgcg ccctgtttgg tccgtggttt cgtgccattg 4320 aaaaagaaat actagccctgctcccgccta atatcttcta cggcgacgcc tacgaggagt 4380 cggtgtttgc cgcggccgtgtccggggcgg ggtcttgcat ggtatttgaa aatgactttt 4440 cggaatttga tagtactcagaacaatttct cccttggcct tgagtgtgtg gttatggaag 4500 agtgtggtat gccccaatggctgatcagat tgtatcacct ggtccggtca gcctggattc 4560 tgcaggcgcc aaaggagtctcttaaaggtt tctggaagaa gcattctggt gagcctggta 4620 cccttctctg gaacaccatctggaacatgg cgatcatagc ccattgctat gagtttcgcg 4680 atttccgggt cgccgcttttaagggtgatg actcggtagt cctctgtagt gattaccgac 4740 agagtcgtaa cgcggcagccttaatcgcag gttgtgggct caagttgaag gttgactatc 4800 gccctattgg gctgtacgctggtgtggtgg tggcccctgg cttggggaca ctgcctgatg 4860 tagtgcgatt tgctggccggctgtccgaaa agaattgggg ccctggccca gagcgtgctg 4920 agcagctgcg tcttgctgtctgtgacttcc ttcgagggtt aacgaatgtt gcgcaggttt 4980 gtgttgatgt tgtgtcccgtgtttatggag tcagccccgg gctggtacat aaccttattg 5040 gcatgctgca gaccattgctgatggcaagg cccactttac agagtcaatt aaacctgtgc 5100 ttgaccttac aaattctattatacagcggg tggaatga 5138 2 15 DNA Hepatitis E virus 2 tgccatggag gccca15 3 15 DNA Hepatitis E virus 3 tkgcgaatgc tgtgg 15 4 15 DNA Hepatitis Evirus 4 rcagtargtg cggtc 15 5 15 DNA Hepatitis E virus 5 cctcsgcracatcag 15 6 15 DNA Hepatitis E virus 6 gtcggtaggg acgtc 15 7 2442 DNAHepatitis E virus 7 tcgatgccat ggaggcccac cagttcatta aggctcctggcattactact gccatagagc 60 aggctgctct ggctgcggcc aactccgcct tggcgaatgctgtggtggtt cggccgtttt 120 tgtctcgcgt acaaaccgag atccttatta atttgatgcaaccccggcag ttggttttcc 180 gccctgaggt gctttggaac catcctattc agagggttatacacaatgaa ttagaacagt 240 actgccgggc ccgggccggt cgttgcctgg agattggggctcatccaaga tctattaatg 300 ataaccccaa tgttttgcac cggtgttttc tcaggccggtcggtagggac gtccagcgct 360 ggtattctgc ccccacccgc ggccctgcag ccaactgccgccgctctgca ttgcgtggcc 420 tcccccctgt cgaccgcact tactgttttg atggattttccagttgtgct ttcgccgcag 480 agaccggcgt ggccctttac tctctacatg acctttggccagctgatgtt gcggaggcta 540 tggcccgcca tggaatgaca cgtctttatg ctgcactccacctccctccc gaggtgttgt 600 taccacccgg tacttaccac acaacctcgt atcttctgatccatgacggc aaccgtgctg 660 ttgtgactta tgaaggtgat actagtgcag gttacaaccatgacgtttcc atacttcgtg 720 catggattcg cacgactaaa atagttggtg accatccgttggttatagag cgtgtgcggg 780 ctattggttg tcattttgtg ctgctgctca ccgcggcccctgagccatcg cccatgcctt 840 acgtccctta cccccgttcc acggaggtgt atgtccgatctatatttggc cctggtggct 900 ccccatcctt gtttccgtca gcttgctcta caaaatctaccttccatgct gttccagttc 960 acatatggga ccggcttatg ctttttggtg ccaccttggacgaccaggcg ttttgctgct 1020 cacggctcat gacatacctc cgtggcatta gctacaaagtcactgtcggt gcgcttgttg 1080 ctaatgaggg gtggaatgcc tctgaagatg ccctcaccgcagtaatcact gcagcctact 1140 tgaccatctg tcaccagcgc tacctccgta cccaggcgatatctaagggt atgcgccggt 1200 tggaggttga gcacgcccag aagtttatta caagactttacagctggtta tttgagaagt 1260 ctggtcgtga ctacatcccc ggccgccaac ttcagttctatgcccagtgc cggcggtggc 1320 tatctgcggg ctttcaccta gaccccagag tgctcgtctttgatgagtca gtgccctgcc 1380 gctgtaggac tttcttaaag aaggttgcgg gtaaattctgttgcttcatg cggtggttag 1440 ggcaggagtg tacttgtttc ttagaaccag ctgagggcttagttggcgat caaggccatg 1500 ataatgaggc ttatgagggt tctgaggttg accaggccgagcctgtacac cttgatgtgt 1560 cggggaccta tgctgtccac gggcaccagc ttgaggccctctacagggca ctcaacattc 1620 cacacgatat tgctgctcga gctgcccgat taacggctactgttgagctc gctgcaggcc 1680 ccgaccgtct ggagtgccgc accgtgctcg ggaacaagactttccggacg acggtgactg 1740 atggcgccca tctagaagcg aacggccctg agcaatatgttctgtcgttc gatgcctccc 1800 gccagtctat gggggccggg tcccatagcc tcacttacgagcttacaccc gccggcttgc 1860 aggttaagat ctcatctaat ggcctagact gcactgccgtattcccccct ggtggcgccc 1920 ctagcgcgcc gccgggggag gtggcggctt tttgcagcgccctctacagg tataacagat 1980 tcacccagcg gcattcgctg accggcggtt tgtggctacatcccgagggg ttgctaggcg 2040 ttttcccccc tttttcccct gggcacattt gggagtctgccaaccccttc tgcggtgagg 2100 gtaccttgta tactcgcacc tggtctacat ctggtttttctagtgacttt tcccctcctg 2160 aggcggccgc ccctgcaccg gctgccgccc cagggtcgtcctcccccact ccaccagtca 2220 gtgatatttg ggtgttacca ccgctttcag aggagccccaggtgggtgcg ccgcctgcac 2280 ctcccacccc cgagcctgct cggctgccct gccccactaaacctaacacc cccgtgcgta 2340 agccaacggc accgccgcct tctcgcaccc gccgccttctttacacctat cctgatggtg 2400 ctaaggtgta tgcggggtca ctgtttgagt cagattgtgatt 2442 8 1703 PRT Hepatitis E virus 8 Met Glu Ala His Gln Phe Ile LysAla Pro Gly Ile Thr Thr Ala Ile 1 5 10 15 Glu Gln Ala Ala Leu Ala AlaAla Asn Ser Ala Leu Ala Asn Ala Val 20 25 30 Val Val Arg Pro Phe Leu SerArg Val Gln Thr Glu Ile Leu Ile Asn 35 40 45 Leu Met Gln Pro Arg Gln LeuVal Phe Arg Pro Glu Val Leu Trp Asn 50 55 60 His Pro Ile Gln Arg Val IleHis Asn Glu Leu Glu Gln Tyr Cys Arg 65 70 75 80 Ala Arg Ala Gly Arg CysLeu Glu Ile Gly Ala His Pro Arg Ser Ile 85 90 95 Asn Asp Asn Pro Asn ValLeu His Arg Cys Phe Leu Arg Pro Val Gly 100 105 110 Arg Asp Val Gln ArgTrp Tyr Ser Ala Pro Thr Arg Gly Pro Ala Ala 115 120 125 Asn Cys Arg ArgSer Ala Leu Arg Gly Leu Pro Pro Val Asp Arg Thr 130 135 140 Tyr Cys PheAsp Gly Phe Ser Ser Cys Ala Phe Ala Ala Glu Thr Gly 145 150 155 160 ValAla Leu Tyr Ser Leu His Asp Leu Trp Pro Ala Asp Val Ala Glu 165 170 175Ala Met Ala Arg His Gly Met Thr Arg Leu Tyr Ala Ala Leu His Leu 180 185190 Pro Pro Glu Val Leu Leu Pro Pro Gly Thr Tyr His Thr Thr Ser Tyr 195200 205 Leu Leu Ile His Asp Gly Asn Arg Ala Val Val Thr Tyr Glu Gly Asp210 215 220 Thr Ser Ala Gly Tyr Asn His Asp Val Ser Ile Leu Arg Ala TrpIle 225 230 235 240 Arg Thr Thr Lys Ile Val Gly Asp His Pro Leu Val IleGlu Arg Val 245 250 255 Arg Ala Ile Gly Cys His Phe Val Leu Leu Leu ThrAla Ala Pro Glu 260 265 270 Pro Ser Pro Met Pro Tyr Val Pro Tyr Pro ArgSer Thr Glu Val Tyr 275 280 285 Val Arg Ser Ile Phe Gly Pro Gly Gly SerPro Ser Leu Phe Pro Ser 290 295 300 Ala Cys Ser Thr Lys Ser Thr Phe HisAla Val Pro Val His Ile Trp 305 310 315 320 Asp Arg Leu Met Leu Phe GlyAla Thr Leu Asp Asp Gln Ala Phe Cys 325 330 335 Cys Ser Arg Leu Met ThrTyr Leu Arg Gly Ile Ser Tyr Lys Val Thr 340 345 350 Val Gly Ala Leu ValAla Asn Glu Gly Trp Asn Ala Ser Glu Asp Ala 355 360 365 Leu Thr Ala ValIle Thr Ala Ala Tyr Leu Thr Ile Cys His Gln Arg 370 375 380 Tyr Leu ArgThr Gln Ala Ile Ser Lys Gly Met Arg Arg Leu Glu Val 385 390 395 400 GluHis Ala Gln Lys Phe Ile Thr Arg Leu Tyr Ser Trp Leu Phe Glu 405 410 415Lys Ser Gly Arg Asp Tyr Ile Pro Gly Arg Gln Leu Gln Phe Tyr Ala 420 425430 Gln Cys Arg Arg Trp Leu Ser Ala Gly Phe His Leu Asp Pro Arg Val 435440 445 Leu Val Phe Asp Glu Ser Val Pro Cys Arg Cys Arg Thr Phe Leu Lys450 455 460 Lys Val Ala Gly Lys Phe Cys Cys Phe Met Arg Trp Leu Gly GlnGlu 465 470 475 480 Cys Thr Cys Phe Leu Glu Pro Ala Glu Gly Leu Val GlyAsp Gln Gly 485 490 495 His Asp Asn Glu Ala Tyr Glu Gly Ser Glu Val AspGln Ala Glu Pro 500 505 510 Val His Leu Asp Val Ser Gly Thr Tyr Ala ValHis Gly His Gln Leu 515 520 525 Glu Ala Leu Tyr Arg Ala Leu Asn Ile ProHis Asp Ile Ala Ala Arg 530 535 540 Ala Ala Arg Leu Thr Ala Thr Val GluLeu Ala Ala Gly Pro Asp Arg 545 550 555 560 Leu Glu Cys Arg Thr Val LeuGly Asn Lys Thr Phe Arg Thr Thr Val 565 570 575 Thr Asp Gly Ala His LeuGlu Ala Asn Gly Pro Glu Gln Tyr Val Leu 580 585 590 Ser Phe Asp Ala SerArg Gln Ser Met Gly Ala Gly Ser His Ser Leu 595 600 605 Thr Tyr Glu LeuThr Pro Ala Gly Leu Gln Val Lys Ile Ser Ser Asn 610 615 620 Gly Leu AspCys Thr Ala Val Phe Pro Pro Gly Gly Ala Pro Ser Ala 625 630 635 640 ProPro Gly Glu Val Ala Ala Phe Cys Ser Ala Leu Tyr Arg Tyr Asn 645 650 655Arg Phe Thr Gln Arg His Ser Leu Thr Gly Gly Leu Trp Leu His Pro 660 665670 Glu Gly Leu Leu Gly Val Phe Pro Pro Phe Ser Pro Gly His Ile Trp 675680 685 Glu Ser Ala Asn Pro Phe Cys Gly Glu Gly Thr Leu Tyr Thr Arg Thr690 695 700 Trp Ser Thr Ser Gly Phe Ser Ser Asp Phe Ser Pro Pro Glu AlaAla 705 710 715 720 Ala Pro Ala Pro Ala Ala Ala Pro Gly Ser Ser Ser ProThr Pro Pro 725 730 735 Val Ser Asp Ile Trp Val Leu Pro Pro Leu Ser GluGlu Pro Gln Val 740 745 750 Gly Ala Pro Pro Ala Pro Pro Thr Pro Glu ProAla Arg Leu Pro Cys 755 760 765 Pro Thr Lys Pro Asn Thr Pro Val Arg LysPro Thr Ala Pro Pro Pro 770 775 780 Ser Arg Thr Arg Arg Leu Leu Tyr ThrTyr Pro Asp Gly Ala Lys Val 785 790 795 800 Tyr Ala Gly Ser Leu Phe GluSer Asp Cys Asp Trp Leu Val Asn Ala 805 810 815 Ser Asn Pro Gly His ArgPro Gly Gly Gly Leu Cys His Ala Phe Tyr 820 825 830 Gln Arg Phe Pro GluAla Phe Tyr Pro Thr Glu Phe Ile Met Arg Glu 835 840 845 Gly Leu Ala AlaTyr Thr Leu Thr Pro Arg Pro Ile Ile His Ala Val 850 855 860 Ala Pro AspTyr Arg Val Glu Gln Asn Pro Lys Arg Leu Glu Ala Ala 865 870 875 880 TyrArg Glu Thr Cys Ser Arg Arg Gly Thr Ala Ala Tyr Pro Leu Leu 885 890 895Gly Ser Gly Ile Tyr Gln Val Pro Ala Gly Leu Ser Phe Asp Ala Trp 900 905910 Glu Arg Asn His Arg Pro Gly Asp Glu Leu Tyr Leu Thr Glu Pro Ala 915920 925 Ala Ala Trp Phe Glu Ala Asn Lys Pro Thr Gln Pro Ala Leu Thr Ile930 935 940 Thr Glu Asp Thr Ala Arg Thr Ala Asn Leu Ala Leu Glu Ile AspAla 945 950 955 960 Ala Thr Asp Val Gly Arg Ala Cys Ala Gly Cys Thr IleSer Pro Gly 965 970 975 Ile Val His Tyr Gln Phe Thr Ala Gly Val Pro GlySer Gly Lys Ser 980 985 990 Arg Ser Ile Gln Gln Gly Asp Val Asp Val ValVal Val Pro Thr Arg 995 1000 1005 Glu Leu Arg Asn Ser Trp Arg Arg ArgGly Phe Ala Ala Phe Thr Pro 1010 1015 1020 His Thr Ala Ala Arg Val ThrIle Gly Arg Arg Val Val Ile Asp Glu 1025 1030 1035 1040 Ala Pro Ser LeuPro Pro His Leu Leu Leu Leu His Met Gln Arg Ala 1045 1050 1055 Ser SerVal His Leu Leu Gly Asp Pro Asn Gln Ile Pro Ala Ile Asp 1060 1065 1070Phe Glu His Ala Gly Leu Val Pro Ala Ile Arg Pro Glu Leu Ala Pro 10751080 1085 Thr Ser Trp Trp His Val Thr His Arg Cys Pro Ala Asp Val CysGlu 1090 1095 1100 Leu Ile Arg Gly Ala Tyr Pro Lys Ile Gln Thr Thr SerArg Val Leu 1105 1110 1115 1120 Arg Ser Leu Phe Trp Asn Glu Pro Ala IleGly Gln Lys Leu Val Phe 1125 1130 1135 Thr Gln Ala Ala Lys Ala Ala AsnPro Gly Ala Ile Thr Val His Glu 1140 1145 1150 Ala Gln Gly Ala Thr PheThr Glu Thr Thr Ile Ile Ala Thr Ala Asp 1155 1160 1165 Ala Arg Gly LeuIle Gln Ser Ser Arg Ala His Ala Ile Val Ala Leu 1170 1175 1180 Thr ArgHis Thr Glu Lys Cys Val Ile Leu Asp Ala Pro Gly Leu Leu 1185 1190 11951200 Arg Glu Val Gly Ile Ser Asp Val Ile Val Asn Asn Phe Phe Leu Ala1205 1210 1215 Gly Gly Glu Val Gly His His Arg Pro Ser Val Ile Pro ArgGly Asn 1220 1225 1230 Pro Asp Arg Asn Leu Asp Thr Leu Gln Ala Phe ProPro Ser Cys Gln 1235 1240 1245 Ile Ser Ala Tyr His Gln Leu Ala Glu GluLeu Gly His Arg Pro Ala 1250 1255 1260 Pro Val Ala Ala Val Leu Pro ProCys Pro Glu Leu Glu Gln Gly Leu 1265 1270 1275 1280 Leu Tyr Met Pro GlnGlu Leu Thr Val Ser Asp Ser Val Leu Val Phe 1285 1290 1295 Glu Leu ThrAsp Ile Val His Cys Arg Met Ala Ala Pro Ser Gln Arg 1300 1305 1310 LysAla Val Leu Ser Thr Leu Val Gly Arg Tyr Gly Arg Lys Thr Lys 1315 13201325 Leu Tyr Glu Ala Ala His Ser Asp Val Arg Glu Ser Leu Ala Arg Phe1330 1335 1340 Ile Pro Thr Ile Gly Pro Val Gln Ala Thr Thr Cys Glu LeuTyr Glu 1345 1350 1355 1360 Leu Val Glu Ala Met Val Glu Lys Gly Gln AspGly Ser Ala Val Leu 1365 1370 1375 Glu Leu Asp Leu Cys Asn Arg Asp ValSer Arg Ile Thr Phe Phe Gln 1380 1385 1390 Lys Asp Cys Asn Lys Phe ThrThr Gly Glu Thr Ile Ala His Gly Lys 1395 1400 1405 Val Gly Gln Gly IleSer Ala Trp Ser Lys Thr Phe Cys Ala Leu Phe 1410 1415 1420 Gly Pro TrpPhe Arg Ala Ile Glu Lys Glu Ile Leu Ala Leu Leu Pro 1425 1430 1435 1440Pro Asn Ile Phe Tyr Gly Asp Ala Tyr Glu Glu Ser Val Phe Ala Ala 14451450 1455 Ala Val Ser Gly Ala Gly Ser Cys Met Val Phe Glu Asn Asp PheSer 1460 1465 1470 Glu Phe Asp Ser Thr Gln Asn Asn Phe Ser Leu Gly LeuGlu Cys Val 1475 1480 1485 Val Met Glu Glu Cys Gly Met Pro Gln Trp LeuIle Arg Leu Tyr His 1490 1495 1500 Leu Val Arg Ser Ala Trp Ile Leu GlnAla Pro Lys Glu Ser Leu Lys 1505 1510 1515 1520 Gly Phe Trp Lys Lys HisSer Gly Glu Pro Gly Thr Leu Leu Trp Asn 1525 1530 1535 Thr Ile Trp AsnMet Ala Ile Ile Ala His Cys Tyr Glu Phe Arg Asp 1540 1545 1550 Phe ArgVal Ala Ala Phe Lys Gly Asp Asp Ser Val Val Leu Cys Ser 1555 1560 1565Asp Tyr Arg Gln Ser Arg Asn Ala Ala Ala Leu Ile Ala Gly Cys Gly 15701575 1580 Leu Lys Leu Lys Val Asp Tyr Arg Pro Ile Gly Leu Tyr Ala GlyVal 1585 1590 1595 1600 Val Val Ala Pro Gly Leu Gly Thr Leu Pro Asp ValVal Arg Phe Ala 1605 1610 1615 Gly Arg Leu Ser Glu Lys Asn Trp Gly ProGly Pro Glu Arg Ala Glu 1620 1625 1630 Gln Leu Arg Leu Ala Val Cys AspPhe Leu Arg Gly Leu Thr Asn Val 1635 1640 1645 Ala Gln Val Cys Val AspVal Val Ser Arg Val Tyr Gly Val Ser Pro 1650 1655 1660 Gly Leu Val HisAsn Leu Ile Gly Met Leu Gln Thr Ile Ala Asp Gly 1665 1670 1675 1680 LysAla His Phe Thr Glu Ser Ile Lys Pro Val Leu Asp Leu Thr Asn 1685 16901695 Ser Ile Ile Gln Arg Val Glu 1700 9 19 DNA Artificial SequenceDescription of Artificial Sequence Hepatitis E virus 9 ttctttctggccccagact 19 10 19 DNA Artificial Sequence Description of ArtificialSequence Hepatitis E virus 10 ttctttctga ccccagact 19 11 7234 DNAHepatitis E virus JSN-FH 11 gtcgacgcca tggaggccca tcagttcata aaggctcctggcgtcacaac tgctattgag 60 caggcagctc tagcagcggc caactccgcc ttggcgaatgctgtggtggt tcggcctttt 120 ctgtcccggc tacagacaga gatacttatt aacttgatgcagccccggca gcttgttttc 180 cggcctgagg tcctgtggaa tcaccccatt caacgcgtgatccacaatga gcttgaacag 240 tactgtcggg ctcgggccgg ccgctgtctt gaagtgggcgctcacccacg ttcgatcaac 300 gacaacccca acgtcttgca tcgctgtttt ttaaaaccagttggccgcga tgtccagcgg 360 tggtacaccg ctcctacccg cggccctgca gcgaactgccgccggtcagc ccttcgtggc 420 ctcccgcctg ttgaccggac atattgcttt gacggtttttccggttgcac atttgccgcc 480 gagacgggga ttgccctcta ctcactgcat gacctttggcctgccgatgt tgctgaggcg 540 atggcccgcc acggtatgac ccggctgtat gcggctctccacctccctcc tgaggtgctg 600 ctcccccctg gtacctatca taccacctcg tacctactcatccatgatgg ggaccgtgca 660 gtgattacat atgaggggga ttctagtgct gggtacaaccatgatgtgtc catcttgcgc 720 gcctggatcc gcactactaa ggttactggt gaccacccgctggtgattga gcgagttcgg 780 gcggtgggtt gtcattttgt gctccttcta acagctgcacctgaaccatc gccaatgccc 840 tatgttccat aycctcgttc cactgaggtt tacgttcggtccatttttgg ccctggtggt 900 tcaccatccc tgtttccaac tgcctgctct actaagtcaacatttcatgc tgtccctgtg 960 catatatggg acagacttat gttattcggt gcgaccctcgacgatcaggc cttttgttgc 1020 tcgaggctaa tgacatacct ccgtggcatt agctacaaagtcacggtcgg cgctcttgtt 1080 gccaacgagg gctggaatgc ctccgaggat gcattgaccgctgtgattac tgcggcctat 1140 cttaccattt gccatcagag gtaccttcgc acgcaggccatctcgaaagg gatgaaaaga 1200 ctggagcttg agcacgcaca gaagttcata acacgtctttacagctggtt gtttgaaaaa 1260 tccggccgtg attacattcc cggccgtcag ctgcagttttatgcccagtg ccgccgatgg 1320 ctttccgctg gtttccatct tgatcctcgt gtgcttgtctttgatgaagc ggccccttgt 1380 cgctgccgta gtttccttcg taaagctgct catagattttgttgttttat gcggtggctg 1440 ggccaggatt gtacctgttt cctccagccc gttgaggggagggttggcga gcagggttac 1500 gataatgagg catttgaggg gtcggatgtt gaccccgctgaggaggccac tgtgaacatc 1560 tctggatcat atattgtcac cggtagccag ctacagcctctctaccaggc gcttggcatc 1620 ccttctgatc ttgccgcccg agcgggtcga cttactgccactgttgaagt cctagatgct 1680 gatggccgcc tcacttgtaa gaccactatt ggcaataagacctttacaac agtttttact 1740 gatggtgctc agctagaggc taacgggccg gagcagtatgtgctgtcgtt tgactcggcc 1800 aagcaaacta tggccgccgg cccgcacagt cttagctatgctttgacatc tgcgggcctt 1860 gaggtgcgcg ttgtctctgc cgggcttgac tgtaaggctgtatttccatc cggggttgca 1920 acccccacca cccctggtga ggtctccgct ttttgttcagctttgtacag gttcaaccgt 1980 tgtgttcagc ggcactccct tattgggggt ttgtggtattaccctgaggg gctaattggc 2040 ttgtttccgc catttgctcc cggccatacc tgggagtcagccaatccctt ctgtggagag 2100 agcaccctct atactcgcac ctggtcggtg tcgggcttctctagttgttt ttctccaccc 2160 gagccacccg ctccagaact atcatctcct gttgaggttgacacacctgt ggctgttggc 2220 gttccatccc cagccacttc ggcagtaccc caaccttcagtccctgaaca ggccgcgcca 2280 ttgccggatt cggttgacgg cggtgctgct ccggccccattgagcacctc tactacaccc 2340 ccggtgccag cgcagcacgt aacccaccca tctggctcccgtcggcggtt acttcacacc 2400 taccctgatg gctcaaaagt gtatgctggc tccctttttgaatctgagtg tacttggtta 2460 gttaatgcat ccaatcctgg tcaccgcccc ggtggcggcctttgccacgc attttaccaa 2520 cggttcccgg agtcatttga ccctgctgag tttattatgtctgacgggtt tgcggcctat 2580 accttgacac cccgacccat tatccatgct gttgcccctgattatcgggt ggaacataac 2640 cctaagaggc tcgaggctgc ctatcgagag acgtgttcccgtcgtgggac ggctgcttat 2700 cccttgcttg gcgccggtat atacagggtg cccgttgggctgagctttga tgcttgggag 2760 cgtaaccacc gacccgggga tgagttgtac ctgactgagccggctatagc ttggttcgag 2820 accaaccgac ctactctccc cgcgcttact attactgaggacacagcacg aacagcgaac 2880 ctggctcttg agttagattc agccactgag gtcggcagggcgtgtgccgg ctgtcgtgtc 2940 gagccgggtg ttgtccatta ccagttcaca gcaggtgtccctggctccgg caagtcacgg 3000 tcaattcagc agggcgaggt agacgtcgta gtggtgccaacccgtgagtt gcgtaactcg 3060 tggcggcgcc gcgggtttgc agcttataca ccacacaccgcggcccgtgt tacctgtggc 3120 cgtagggttg ttattgacga ggccccgtcg cttccaccacatttactttt gctgcatatg 3180 cagcgagcct cgtcggttca tctccttggc gaccccaaccaaatccctgc tatcgatttt 3240 gagcatgctg gcctcgttcc ggcgatccgg cctgagcttgttccaacaaa gtggtggcac 3300 cttactcata ggtgtcctgc ggatgtttgt gagctaatccgcggcgcgta cccaaagatc 3360 cagacggcaa gccgagttct ccgctccctg ttctggggggagccccccgt tggccaaaaa 3420 ctagtgttta ctcaggcggc gaaggccgcc aaccccggtgcaattacagt ccacgaggcc 3480 cagggtgcta catttactga gactactatt attgcaacggctgatgcccg cgggctgatt 3540 cagtcctcca gggcccacgc tattgtggcc ctgactcgccacacagagaa atgtgtggtc 3600 gttgacgccc cggggcttct tcgtgaggtt ggcatttcagatgccattgt taataacttt 3660 tttctttctg gcggccaggt tggtcagcac cgcccatcagtcatacctcg tggcactgtt 3720 gatagcaatg ttgccacgct tgatgcattt ccaccttcttgtcaatttag cgcctatcac 3780 cagcttgcag aggagcttgg tcatcggccg gccccgattgccgccgttct gcccccttgt 3840 ccggagctcg agcaaggctt actctatatg ccccaggaactgaccacgtc cgatagtgtg 3900 ctcacattcg aacttacaga cattgtacac tgtcgtatggcggcacctag tcagcgcaaa 3960 gcagtcctgt cgacccttgt cggcaggtac ggccgccgtacgaagttgta tgaagctgct 4020 cacacggatg ttcgtgggtc cctctgtcat tttctccccgagcttggccc catcagcgtt 4080 actacctgcg agctttatga gcttgttgag gctatggtggagaagggtca ggatggctct 4140 gcagtcttgg aactcgatct atgcagtcgt gatgtgtcacgtataacatt cttccagaag 4200 gactgtaata aattcacaac aggcgagaca atagcgcacggtaaagttgg gcaggggata 4260 tctgcgtgga gcaagacctt ttgtgccctg tttggcccatggttccgcgc tattgagaag 4320 gagattcttg cggcgcttgc ccctaatgta ttttatggtgatgcatatga agatacagtt 4380 ttggccgccg ctgtcgccgg ggccccaggc tgtaaggtttttgagaatga tttctctgag 4440 tttgacagca cccaaaataa cttttcactc ggactggagtgcataatcat ggaggaatgt 4500 ggcatgccgc agtggatgat ccgactttat catcttgttcgctccgcctg ggtcctgcag 4560 gctcccaagg agtccctgcg agggttctgg aagaagcactcgggcgagcc tggcactctg 4620 ctctggaaca ctgtctggaa catggcggtt attgcgcattgttatgaatt ccgtgaccta 4680 aaggtcgcgg catttaaagg agatgactca gttgtgctctgtagtgacta ccggcagagc 4740 cgcaacgctg ctgctctaat cgccggttgc gggttgaaacttaaggtgga ttttaggcct 4800 attgggctat atgctggtgt tgttgtggcc ccgggcctcgggaccctccc tgatgtcgtt 4860 aggtttgctg ggcggctctc agagaaaaac tgggggccgggttcagagag ggcggaacag 4920 ctacggctgg ccgtttgtga ttttctgcga aagttaacgaatgtggctca ggtctgtgtg 4980 gatgttgttt cgcaggttta tggtgtcagc cccggtttagtacataacct gattggaatg 5040 ctccagacca ttgctgatgg taaggcgcat tttactgaaacagtcaaacc cgtccttgat 5100 cttactagct ctattatata ccgggtggaa tgaataacatgttcttttgc tctgtgcatg 5160 gagatgccac catgcgctct cgggctcttc tgtttctgctcttcgtgctt ctgcctatgc 5220 tgcccgcgcc accggccggt cagccgtctg gccgtcgccgcgggcggcgc agcggcggtg 5280 ccggcggtgg tttctggggt gaccgggttg attctcagcccttcgccctc ccctatattc 5340 atccaaccaa ccccttcgca tctgacatac caaccgcagccgggtctgga gctcgccctc 5400 ggcagccggc ccgtccactc ggctccgctt ggcgtgaccagtcccagcgc cccgccgctc 5460 ccgcccgccg tcgatctgcc ccagctgggg cttcgccgctgactgctgtg gccccggccc 5520 ctgataccgc ccctgtgccc gacgttgact cccgcggcgctatactacgc cgccagtata 5580 atctatcaac atccccgctt acgtctacca tcgctactggcaccaatctt gttttatatg 5640 ctgctcccct tagccctctg cttccgcttc aagatgggactaacactcat attatggcca 5700 ctgaagcatc aaattacgcc cagtaccgcg ttgtccgtgccaccatccgg tatcgcccac 5760 ttgtgccgaa tgctgttggc gggtacgcta tatctatttctttctggccc cagactacaa 5820 ctaccccaac atctgtcgat atgaattcta ttacctctactgatgttcgg attcttgttc 5880 agcctggtat cgcctccgag cttgtgattc ccagtgagcgcctgcactac cgcaatcagg 5940 gctggcgctc ggttgagacc tctggtgtcg cggaggaggaggcgacctcc ggccttgtta 6000 tgctctgcat ccatggatca cctgtgaact cttacactaatacaccttac actggtgctc 6060 ttggcttact cgatttcgca cttgaacttg agttccgtaatttgacaccc ggtaacacga 6120 atacgcgcgt ttcccgttat tcgagtagcg cgcgccacaagctacgtcgt gggcccgacg 6180 gtactgctga gctaaccacc actgctgcta cacggtttatgaaagatctt cacttcacag 6240 ggaccaatgg tgttggtgag gtcggtcgcg gtatagcgctaactctgttt aatcttgctg 6300 acacgcttct cggcgggctc ccgacagaat tgatttcgtcggctggtggc cagctatttt 6360 actctcgccc cgtcgtctca gccaatggcg agccgacagtgaagctttac acttcagtcg 6420 agaacgccca gcaggataag ggtatagcta ttccacatgatatcgacctt ggtgagtctc 6480 gagttgtcat ccaggattac gataaccagc acgagcaggaccgtcccacc ccgtctccag 6540 ccccttcccg ccctttttct gtcctccgcg ctaatgatgtgctttggctc tcacttacag 6600 ctgctgagta tgatcagact acttatggtt cttccactaatcctatgtat gtctctgata 6660 ctgtgacatt tgtcaatgtg gcgactggtg ctcagggggtctctcgctct ctggactggt 6720 ctaaagtcac ccttgatggg cgtccactta ctactatccagcagtactct aagaccttct 6780 ttgttctgcc cctccgtggc aagctctctt tctgggaggctggcaccact aaggccggct 6840 acccttataa ttataatacc actgccagtg accagatcttgattgaaaat gcagccggtc 6900 accgtgtttg tatctcaacc tacactacta atcttggctctggccctgtt tctatttctt 6960 ctgtcggtgt ccttgcacct cattctgcgc tggccgctttagaggacact gttgattatc 7020 ctgctcgcgc ccacaccttt gatgatttct gccctgagtgccgtacgctc ggccttcagg 7080 gctgtgcttt tcaatcaact gttgctgagc tgcagcgtcttaaaatgaag gtgggtaaaa 7140 cccgggagta ttgatttatt gtgcttgtac cttccttctgatttgtttct tttatttcct 7200 tcttctgcgt ttcgcgctcc ctggaaaaaa aaaa 7234 121707 PRT Hepatitis E virus JSN-FH ORF1 MISC_FEATURE (281)..(281) X ISANY ONE AMINO ACID 12 Met Glu Ala His Gln Phe Ile Lys Ala Pro Gly ValThr Thr Ala Ile 1 5 10 15 Glu Gln Ala Ala Leu Ala Ala Ala Asn Ser AlaLeu Ala Asn Ala Val 20 25 30 Val Val Arg Pro Phe Leu Ser Arg Leu Gln ThrGlu Ile Leu Ile Asn 35 40 45 Leu Met Gln Pro Arg Gln Leu Val Phe Arg ProGlu Val Leu Trp Asn 50 55 60 His Pro Ile Gln Arg Val Ile His Asn Glu LeuGlu Gln Tyr Cys Arg 65 70 75 80 Ala Arg Ala Gly Arg Cys Leu Glu Val GlyAla His Pro Arg Ser Ile 85 90 95 Asn Asp Asn Pro Asn Val Leu His Arg CysPhe Leu Lys Pro Val Gly 100 105 110 Arg Asp Val Gln Arg Trp Tyr Thr AlaPro Thr Arg Gly Pro Ala Ala 115 120 125 Asn Cys Arg Arg Ser Ala Leu ArgGly Leu Pro Pro Val Asp Arg Thr 130 135 140 Tyr Cys Phe Asp Gly Phe SerGly Cys Thr Phe Ala Ala Glu Thr Gly 145 150 155 160 Ile Ala Leu Tyr SerLeu His Asp Leu Trp Pro Ala Asp Val Ala Glu 165 170 175 Ala Met Ala ArgHis Gly Met Thr Arg Leu Tyr Ala Ala Leu His Leu 180 185 190 Pro Pro GluVal Leu Leu Pro Pro Gly Thr Tyr His Thr Thr Ser Tyr 195 200 205 Leu LeuIle His Asp Gly Asp Arg Ala Val Ile Thr Tyr Glu Gly Asp 210 215 220 SerSer Ala Gly Tyr Asn His Asp Val Ser Ile Leu Arg Ala Trp Ile 225 230 235240 Arg Thr Thr Lys Val Thr Gly Asp His Pro Leu Val Ile Glu Arg Val 245250 255 Arg Ala Val Gly Cys His Phe Val Leu Leu Leu Thr Ala Ala Pro Glu260 265 270 Pro Ser Pro Met Pro Tyr Val Pro Xaa Pro Arg Ser Thr Glu ValTyr 275 280 285 Val Arg Ser Ile Phe Gly Pro Gly Gly Ser Pro Ser Leu PhePro Thr 290 295 300 Ala Cys Ser Thr Lys Ser Thr Phe His Ala Val Pro ValHis Ile Trp 305 310 315 320 Asp Arg Leu Met Leu Phe Gly Ala Thr Leu AspAsp Gln Ala Phe Cys 325 330 335 Cys Ser Arg Leu Met Thr Tyr Leu Arg GlyIle Ser Tyr Lys Val Thr 340 345 350 Val Gly Ala Leu Val Ala Asn Glu GlyTrp Asn Ala Ser Glu Asp Ala 355 360 365 Leu Thr Ala Val Ile Thr Ala AlaTyr Leu Thr Ile Cys His Gln Arg 370 375 380 Tyr Leu Arg Thr Gln Ala IleSer Lys Gly Met Lys Arg Leu Glu Leu 385 390 395 400 Glu His Ala Gln LysPhe Ile Thr Arg Leu Tyr Ser Trp Leu Phe Glu 405 410 415 Lys Ser Gly ArgAsp Tyr Ile Pro Gly Arg Gln Leu Gln Phe Tyr Ala 420 425 430 Gln Cys ArgArg Trp Leu Ser Ala Gly Phe His Leu Asp Pro Arg Val 435 440 445 Leu ValPhe Asp Glu Ala Ala Pro Cys Arg Cys Arg Ser Phe Leu Arg 450 455 460 LysAla Ala His Arg Phe Cys Cys Phe Met Arg Trp Leu Gly Gln Asp 465 470 475480 Cys Thr Cys Phe Leu Gln Pro Val Glu Gly Arg Val Gly Glu Gln Gly 485490 495 Tyr Asp Asn Glu Ala Phe Glu Gly Ser Asp Val Asp Pro Ala Glu Glu500 505 510 Ala Thr Val Asn Ile Ser Gly Ser Tyr Ile Val Thr Gly Ser GlnLeu 515 520 525 Gln Pro Leu Tyr Gln Ala Leu Gly Ile Pro Ser Asp Leu AlaAla Arg 530 535 540 Ala Gly Arg Leu Thr Ala Thr Val Glu Val Leu Asp AlaAsp Gly Arg 545 550 555 560 Leu Thr Cys Lys Thr Thr Ile Gly Asn Lys ThrPhe Thr Thr Val Phe 565 570 575 Thr Asp Gly Ala Gln Leu Glu Ala Asn GlyPro Glu Gln Tyr Val Leu 580 585 590 Ser Phe Asp Ser Ala Lys Gln Thr MetAla Ala Gly Pro His Ser Leu 595 600 605 Ser Tyr Ala Leu Thr Ser Ala GlyLeu Glu Val Arg Val Val Ser Ala 610 615 620 Gly Leu Asp Cys Lys Ala ValPhe Pro Ser Gly Val Ala Thr Pro Thr 625 630 635 640 Thr Pro Gly Glu ValSer Ala Phe Cys Ser Ala Leu Tyr Arg Phe Asn 645 650 655 Arg Cys Val GlnArg His Ser Leu Ile Gly Gly Leu Trp Tyr Tyr Pro 660 665 670 Glu Gly LeuIle Gly Leu Phe Pro Pro Phe Ala Pro Gly His Thr Trp 675 680 685 Glu SerAla Asn Pro Phe Cys Gly Glu Ser Thr Leu Tyr Thr Arg Thr 690 695 700 TrpSer Val Ser Gly Phe Ser Ser Cys Phe Ser Pro Pro Glu Pro Pro 705 710 715720 Ala Pro Glu Leu Ser Ser Pro Val Glu Val Asp Thr Pro Val Ala Val 725730 735 Gly Val Pro Ser Pro Ala Thr Ser Ala Val Pro Gln Pro Ser Val Pro740 745 750 Glu Gln Ala Ala Pro Leu Pro Asp Ser Val Asp Gly Gly Ala AlaPro 755 760 765 Ala Pro Leu Ser Thr Ser Thr Thr Pro Pro Val Pro Ala GlnHis Val 770 775 780 Thr His Pro Ser Gly Ser Arg Arg Arg Leu Leu His ThrTyr Pro Asp 785 790 795 800 Gly Ser Lys Val Tyr Ala Gly Ser Leu Phe GluSer Glu Cys Thr Trp 805 810 815 Leu Val Asn Ala Ser Asn Pro Gly His ArgPro Gly Gly Gly Leu Cys 820 825 830 His Ala Phe Tyr Gln Arg Phe Pro GluSer Phe Asp Pro Ala Glu Phe 835 840 845 Ile Met Ser Asp Gly Phe Ala AlaTyr Thr Leu Thr Pro Arg Pro Ile 850 855 860 Ile His Ala Val Ala Pro AspTyr Arg Val Glu His Asn Pro Lys Arg 865 870 875 880 Leu Glu Ala Ala TyrArg Glu Thr Cys Ser Arg Arg Gly Thr Ala Ala 885 890 895 Tyr Pro Leu LeuGly Ala Gly Ile Tyr Arg Val Pro Val Gly Leu Ser 900 905 910 Phe Asp AlaTrp Glu Arg Asn His Arg Pro Gly Asp Glu Leu Tyr Leu 915 920 925 Thr GluPro Ala Ile Ala Trp Phe Glu Thr Asn Arg Pro Thr Leu Pro 930 935 940 AlaLeu Thr Ile Thr Glu Asp Thr Ala Arg Thr Ala Asn Leu Ala Leu 945 950 955960 Glu Leu Asp Ser Ala Thr Glu Val Gly Arg Ala Cys Ala Gly Cys Arg 965970 975 Val Glu Pro Gly Val Val His Tyr Gln Phe Thr Ala Gly Val Pro Gly980 985 990 Ser Gly Lys Ser Arg Ser Ile Gln Gln Gly Glu Val Asp Val ValVal 995 1000 1005 Val Pro Thr Arg Glu Leu Arg Asn Ser Trp Arg Arg ArgGly Phe Ala 1010 1015 1020 Ala Tyr Thr Pro His Thr Ala Ala Arg Val ThrCys Gly Arg Arg Val 1025 1030 1035 1040 Val Ile Asp Glu Ala Pro Ser LeuPro Pro His Leu Leu Leu Leu His 1045 1050 1055 Met Gln Arg Ala Ser SerVal His Leu Leu Gly Asp Pro Asn Gln Ile 1060 1065 1070 Pro Ala Ile AspPhe Glu His Ala Gly Leu Val Pro Ala Ile Arg Pro 1075 1080 1085 Glu LeuVal Pro Thr Lys Trp Trp His Leu Thr His Arg Cys Pro Ala 1090 1095 1100Asp Val Cys Glu Leu Ile Arg Gly Ala Tyr Pro Lys Ile Gln Thr Ala 11051110 1115 1120 Ser Arg Val Leu Arg Ser Leu Phe Trp Gly Glu Pro Pro ValGly Gln 1125 1130 1135 Lys Leu Val Phe Thr Gln Ala Ala Lys Ala Ala AsnPro Gly Ala Ile 1140 1145 1150 Thr Val His Glu Ala Gln Gly Ala Thr PheThr Glu Thr Thr Ile Ile 1155 1160 1165 Ala Thr Ala Asp Ala Arg Gly LeuIle Gln Ser Ser Arg Ala His Ala 1170 1175 1180 Ile Val Ala Leu Thr ArgHis Thr Glu Lys Cys Val Val Val Asp Ala 1185 1190 1195 1200 Pro Gly LeuLeu Arg Glu Val Gly Ile Ser Asp Ala Ile Val Asn Asn 1205 1210 1215 PhePhe Leu Ser Gly Gly Gln Val Gly Gln His Arg Pro Ser Val Ile 1220 12251230 Pro Arg Gly Thr Val Asp Ser Asn Val Ala Thr Leu Asp Ala Phe Pro1235 1240 1245 Pro Ser Cys Gln Phe Ser Ala Tyr His Gln Leu Ala Glu GluLeu Gly 1250 1255 1260 His Arg Pro Ala Pro Ile Ala Ala Val Leu Pro ProCys Pro Glu Leu 1265 1270 1275 1280 Glu Gln Gly Leu Leu Tyr Met Pro GlnGlu Leu Thr Thr Ser Asp Ser 1285 1290 1295 Val Leu Thr Phe Glu Leu ThrAsp Ile Val His Cys Arg Met Ala Ala 1300 1305 1310 Pro Ser Gln Arg LysAla Val Leu Ser Thr Leu Val Gly Arg Tyr Gly 1315 1320 1325 Arg Arg ThrLys Leu Tyr Glu Ala Ala His Thr Asp Val Arg Gly Ser 1330 1335 1340 LeuCys His Phe Leu Pro Glu Leu Gly Pro Ile Ser Val Thr Thr Cys 1345 13501355 1360 Glu Leu Tyr Glu Leu Val Glu Ala Met Val Glu Lys Gly Gln AspGly 1365 1370 1375 Ser Ala Val Leu Glu Leu Asp Leu Cys Ser Arg Asp ValSer Arg Ile 1380 1385 1390 Thr Phe Phe Gln Lys Asp Cys Asn Lys Phe ThrThr Gly Glu Thr Ile 1395 1400 1405 Ala His Gly Lys Val Gly Gln Gly IleSer Ala Trp Ser Lys Thr Phe 1410 1415 1420 Cys Ala Leu Phe Gly Pro TrpPhe Arg Ala Ile Glu Lys Glu Ile Leu 1425 1430 1435 1440 Ala Ala Leu AlaPro Asn Val Phe Tyr Gly Asp Ala Tyr Glu Asp Thr 1445 1450 1455 Val LeuAla Ala Ala Val Ala Gly Ala Pro Gly Cys Lys Val Phe Glu 1460 1465 1470Asn Asp Phe Ser Glu Phe Asp Ser Thr Gln Asn Asn Phe Ser Leu Gly 14751480 1485 Leu Glu Cys Ile Ile Met Glu Glu Cys Gly Met Pro Gln Trp MetIle 1490 1495 1500 Arg Leu Tyr His Leu Val Arg Ser Ala Trp Val Leu GlnAla Pro Lys 1505 1510 1515 1520 Glu Ser Leu Arg Gly Phe Trp Lys Lys HisSer Gly Glu Pro Gly Thr 1525 1530 1535 Leu Leu Trp Asn Thr Val Trp AsnMet Ala Val Ile Ala His Cys Tyr 1540 1545 1550 Glu Phe Arg Asp Leu LysVal Ala Ala Phe Lys Gly Asp Asp Ser Val 1555 1560 1565 Val Leu Cys SerAsp Tyr Arg Gln Ser Arg Asn Ala Ala Ala Leu Ile 1570 1575 1580 Ala GlyCys Gly Leu Lys Leu Lys Val Asp Phe Arg Pro Ile Gly Leu 1585 1590 15951600 Tyr Ala Gly Val Val Val Ala Pro Gly Leu Gly Thr Leu Pro Asp Val1605 1610 1615 Val Arg Phe Ala Gly Arg Leu Ser Glu Lys Asn Trp Gly ProGly Ser 1620 1625 1630 Glu Arg Ala Glu Gln Leu Arg Leu Ala Val Cys AspPhe Leu Arg Lys 1635 1640 1645 Leu Thr Asn Val Ala Gln Val Cys Val AspVal Val Ser Gln Val Tyr 1650 1655 1660 Gly Val Ser Pro Gly Leu Val HisAsn Leu Ile Gly Met Leu Gln Thr 1665 1670 1675 1680 Ile Ala Asp Gly LysAla His Phe Thr Glu Thr Val Lys Pro Val Leu 1685 1690 1695 Asp Leu ThrSer Ser Ile Ile Tyr Arg Val Glu 1700 1705 13 211 PRT Hepatitis E virusJSN-FH ORF2(1-211) 13 Met Arg Ser Arg Ala Leu Leu Phe Leu Leu Phe ValLeu Leu Pro Met 1 5 10 15 Leu Pro Ala Pro Pro Ala Gly Gln Pro Ser GlyArg Arg Arg Gly Arg 20 25 30 Arg Ser Gly Gly Ala Gly Gly Gly Phe Trp GlyAsp Arg Val Asp Ser 35 40 45 Gln Pro Phe Ala Leu Pro Tyr Ile His Pro ThrAsn Pro Phe Ala Ser 50 55 60 Asp Ile Pro Thr Ala Ala Gly Ser Gly Ala ArgPro Arg Gln Pro Ala 65 70 75 80 Arg Pro Leu Gly Ser Ala Trp Arg Asp GlnSer Gln Arg Pro Ala Ala 85 90 95 Pro Ala Arg Arg Arg Ser Ala Pro Ala GlyAla Ser Pro Leu Thr Ala 100 105 110 Val Ala Pro Ala Pro Asp Thr Ala ProVal Pro Asp Val Asp Ser Arg 115 120 125 Gly Ala Ile Leu Arg Arg Gln TyrAsn Leu Ser Thr Ser Pro Leu Thr 130 135 140 Ser Thr Ile Ala Thr Gly ThrAsn Leu Val Leu Tyr Ala Ala Pro Leu 145 150 155 160 Ser Pro Leu Leu ProLeu Gln Asp Gly Thr Asn Thr His Ile Met Ala 165 170 175 Thr Glu Ala SerAsn Tyr Ala Gln Tyr Arg Val Val Arg Ala Thr Ile 180 185 190 Arg Tyr ArgPro Leu Val Pro Asn Ala Val Gly Gly Tyr Ala Ile Ser 195 200 205 Ile SerPhe 210 14 2582 DNA Hepatitis E virus Mexico (M74506) 14 gccatggaggcccaccagtt cattaaggct cctggcatca ctactgctat tgagcaagca 60 gctctagcagcggccaactc cgcccttgcg aatgctgtgg tggtccggcc tttcctttcc 120 catcagcaggttgagatcct tataaatctc atgcaacctc ggcagctggt gtttcgtcct 180 gaggttttttggaatcaccc gattcaacgt gttatacata atgagcttga gcagtattgc 240 cgtgctcgctcgggtcgctg ccttgagatt ggagcccacc cacgctccat taatgataat 300 cctaatgtcctccatcgctg ctttctccac cccgtcggcc gggatgttca gcgctggtac 360 acagccccgactaggggacc tgcggcgaac tgtcgccgct cggcacttcg tggtctgcca 420 ccagccgaccgcacttactg ttttgatggc tttgccggct gccgttttgc cgccgagact 480 ggtgtggctctctattctct ccatgacttg cagccggctg atgttgccga ggcgatggct 540 cgccacggcatgacccgcct ttatgcagct ttccacttgc ctccagaggt gctcctgcct 600 cctggcacctaccggacatc atcctacttg ctgatccacg atggtaagcg cgcggttgtc 660 acttatgagggtgacactag cgccggttac aatcatgatg ttgccaccct ccgcacatgg 720 atcaggacaactaaggttgt gggtgaacac cctttggtga tcgagcgggt gcggggtatt 780 ggctgtcactttgtgttgtt gatcactgcg gcccctgagc cctccccgat gccctacgtt 840 ccttacccgcgttcgacgga ggtctatgtc cggtctatct ttgggcccgg cgggtccccg 900 tcgctgttcccgaccgcttg tgctgtcaag tccacttttc acgccgtccc cacgcacatc 960 tgggaccgtctcatgctctt tggggccacc ctcgacgacc aggccttttg ctgctccagg 1020 cttatgacgtaccttcgtgg cattagctat aaggtaactg tgggtgccct ggtcgctaat 1080 gaaggctggaatgccaccga ggatgcgctc actgcagtta ttacggcggc ttacctcaca 1140 atatgtcatcagcgttattt gcggacccag gcgatttcta agggcatgcg ccggcttgag 1200 cttgaacatgctcagaaatt tatttcacgc ctctacagct ggctatttga gaagtcaggt 1260 cgtgattacatcccaggccg ccagctgcag ttctacgctc agtgccgccg ctggttatct 1320 gccgggttccatctcgaccc ccgcacctta gtttttgatg agtcagtgcc ttgtagctgc 1380 cgaaccaccatccggcggat cgctggaaaa ttttgctgtt ttatgaagtg gctcggtcag 1440 gagtgttcttgtttcctcca gcccgccgag gggctggcgg gcgaccaagg tcatgacaat 1500 gaggcctatgaaggctctga tgttgatact gctgagcctg ccaccctaga cattacaggc 1560 tcatacatcgtggatggtcg gtctctgcaa actgtctatc aagctctcga cctgccagct 1620 gacctggtagctcgcgcagc ccgactgtct gctacagtta ctgttactga aacctctggc 1680 cgtctggattgccaaacaat gatcggcaat aagacttttc tcactacctt tgttgatggg 1740 gcacgccttgaggttaacgg gcctgagcag cttaacctct cttttgacag ccagcagtgt 1800 agtatggcagccggcccgtt ttgcctcacc tatgctgccg tagatggcgg gctggaagtt 1860 catttttccaccgctggcct cgagagccgt gttgttttcc cccctggtaa tgccccgact 1920 gccccgccgagtgaggtcac cgccttctgc tcagctcttt ataggcacaa ccggcagagc 1980 cagcgccagtcggttattgg tagtttgtgg ctgcaccctg aaggtttgct cggcctgttc 2040 ccgcccttttcacccgggca tgagtggcgg tctgctaacc cattttgcgg cgagagcacg 2100 ctctacacccgcacttggtc cacaattaca gacacaccct taactgtcgg gctaatttcc 2160 ggtcatttggatgctgctcc ccactcgggg gggccacctg ctactgccac aggccctgct 2220 gtaggctcgtctgactctcc agaccctgac ccgctacctg atgttacaga tggctcacgc 2280 ccctctggggcccgtccggc tggccccaac ccgaatggcg ttccgcagcg ccgcttacta 2340 cacacctaccctgacggcgc taagatctat gtcggctcca ttttcgagtc tgagtgcacc 2400 tggcttgtcaacgcatctaa cgccggccac cgccctggtg gcgggctttg tcatgctttt 2460 tttcagcgttaccctgattc gtttgacgcc accaagtttg tgatgcgtga tggtcttgcc 2520 gcgtatacccttacaccccg gccgatcatt catgcggtgg ccccggacta tcgattggaa 2580 ca 2582 15255 DNA Hepatitis E virus Japan JRA1(AP003430) 15 ggcagaccac gtatgtggtcgatgccatgg aggcccacca gttcattaag gctcctggca 60 ttactactgc catagagcaggctgctctgg ctgcggccaa ctccgccttg gcgaatgctg 120 tggtggttcg gccgtttttgtctcgcgtac aaaccgagat ccttattaat ttgatgcaac 180 cccggcagtt ggttttccgccctgaggtgc tttggaacca tcctattcag agggttatac 240 acaatgaatt agaac 255 16254 DNA Hepatitis E virus Japan JKN-Sap(AB074918) 16 gcagaccacgtatgtggtcg atgccatgga ggcccatcag ttcattaagg ctcctggcat 60 tactactgccattgagcagg ctgctctggc tgcggccaat tccgccttgg cgaatgctgt 120 ggtggtccggccgttcttat ctcgtgtaca aactgagatt cttattaatt tgatgcaacc 180 ccggcagttggttttccgcc ctgaggtgct ctggaatcac cctatccagc gggttataca 240 taatgaattggaac 254 17 238 DNA Hepatitis E virus JMY-Haw(AB074920) 17 gtcgatgccatggaggccca tcaattcatt aaggctcctg gcattactac tgccattgag 60 caggctgctctggctgcggc caattccgcc ttggcgaatg ctgtggtggt ccggccgttt 120 ttatctcgtgtacaaaccga gattcttatt aatttgatgc aaccccggca gttggttttc 180 cgtcctgaggtgctctggaa tcatcctatt cagcgggtta tacataatga attggaac 238 18 264 DNAHepatitis E virus USA US-1(AF060669) 18 tcgacagggg gcagaccacg tatgtggtcgatgccatgga ggcccatcag ttcattaagg 60 ctcctggcat tactactgct attgagcaggctgctctggc tgcggctaat tccgccttgg 120 cgaatgctgt ggtggttcgg ccgtttctttctcgtgtgca aactgagatt cttattaatt 180 tgatgcaacc ccggcagttg gtcttccgccctgaggtgct ttggaatcat cctatccagc 240 gggttataca taatgaatta gagc 264 19238 DNA Hepatitis E virus SWINE HEV(AF082843) 19 ttcgatgcca tggaggcccatcagttcatt aaggctcctg gcattactac tgccattgag 60 caggctgctc tggctgcggccaactccgcc ttggcgaatg ctgtggtggt tcggccgttt 120 ttatctcgtg tacaaactgagatccttatt aatttgatgc aaccccggca gttggttttc 180 cgccctgagg tactttggaatcatcctatc cagcgggcaa tacataatga actggaac 238 20 238 DNA Hepatitis Evirus Japan JAK-Sai(AB074915) 20 gtcgacgcca tggaggccca tcagtttataaaggctcctg gcgtcactac tgctattgag 60 caggcagctc tagcagcggc caactccgccttggcgaatg ctgtggtggt tcggcctttc 120 ttatcccggc tacagacaga gatactcattaacctgatgc agccccggca gcttgttttc 180 cggcctgagg ttttatggaa tcacccaattcagcgtgtga tccacaatga gctcgaac 238 21 238 DNA Hepatitis E virus JapanJKK-Sap(AB074917) 21 gtcgacgcca tggaggccca ccagttcata aaggctcctggcgtcactac tgctattgag 60 caggcagctc tagcagcggc caactccgcc ttggcgaatgctgtggtggt tcggcctttc 120 ctatcccggc tacagacaga gatacttatt aacctgatgcagccccggca gcttgttttc 180 cggcctgaag tcttgtggaa ccacccaatt cagcgcgtgatccacaacga gcttgagc 238 22 238 DNA Hepatitis E virus Japan JSN-FH 22gtcgacgcca tggaggccca tcagttcata aaggctcctg gcgtcacaac tgctattgag 60caggcagctc tagcagcggc caactccgcc ttggcgaatg ctgtggtggt tcggcctttt 120ctgtcccggc tacagacaga gatacttatt aacttgatgc agccccggca gcttgttttc 180cggcctgagg tcctgtggaa tcaccccatt caacgcgtga tccacaatga gcttgaac 238 23254 DNA Hepatitis E virus China type4(AJ272108) 23 gcagaccacg tatgtggtcgacgccatgga ggcccaccag tttataaagg ctcctggcgt 60 cactactgct attgagcaggcagctctagc agcggccaac tccgccctgg cgaatgctgt 120 ggtggttcgg cctttcttgtcccggcttca gactgagatt ctcataaatt tgatgcagcc 180 ttggcagctt gttttccggcctgaggtcct gtggaatcac ccaatccagc gtgtgatcca 240 caatgagctt gagc 254 24256 DNA Hepatitis E virus Burma B1(M73218) 24 aggcagacca catatgtggtcgatgccatg gaggcccatc agtttattaa ggctcctggc 60 atcactactg ctattgagcaggctgctcta gcagcggcca actctgccct ggcgaatgct 120 gtggtagtta ggccttttctctctcaccag cagattgaga tcctcattaa cctaatgcaa 180 cctcgccagc ttgttttccgccccgaggtt ttctggaatc atcccatcca gcgtgtcatc 240 cataacgagc tggagc 256 25256 DNA Hepatitis E virus China Uigh(D11093) 25 aggcagacca catatgtggtcgatgccatg gaggcccatc agtttatcaa ggctcctggc 60 atcactactg ctattgagcaggctgctcta gcagcggcca attctgccct tgcgaatgct 120 gtggtagtta ggccttttctctctcaccag cagattgaga tccttattaa cctaatgcaa 180 cctcgccagc ttgttttccgccccgaggtt ttctggaacc accccatcca gcgtgtcatc 240 cataatgagc tggagc 256 26256 DNA Hepatitis E virus China Hebei(M94177) 26 aggcagacca catatgtggtcgatgccatg gaggcccatc agtttattaa ggctcctggc 60 atcactactg ctattgagcaggctgctcta gcagcggcca actctgccct tgcgaatgct 120 gtggtagtta ggccttttctctctcaccag cagattgaga tccttattaa cctaatgcaa 180 cctcgccagc ttgttttccgccccgaggtt ttctggaacc atcccatcca gcgtgttatc 240 cataatgagc tggagc 256 27256 DNA Hepatitis E virus China Xinjiang(D11092) 27 aggcagaccacatatgtggt cgatgccatg gaggcccatc agtttatcaa ggctcctggc 60 atcactactgctattgagca ggctgctcta gcagcggcca actctgccct tgcgaatgct 120 gtggtagttaggccttttct ctctcaccag cagattgaga tccttattaa cctaatgcaa 180 ccccgccagcttgttttccg ccccgaggtt ttctggaacc atcccatcca gcgtgttatc 240 cataatgagctggagc 256 28 256 DNA Hepatitis E virus Nepali(AF051830) 28 aggcagaccacatatgtggt cgatgccatg gaggcccatc agtttattaa ggctcctggc 60 atcactactgctattgagca ggctgctcta gcagcggcca actctgccct ggcgaatgct 120 gtggtagttaggccttttct ctctcaccag cagattgaga ttctcattaa cctaatgcaa 180 cctcgccagcttgttttccg ccccgaggtt ttctggaatc atcccatcca gcgtgtcatc 240 cataacgagctggagc 256 29 255 DNA Hepatitis E virus India FH strain(X98292) 29ggcagaccac ctatgtggtc gatgccatgg aggcccatca gtttatcaag gctcctggca 60tcactactgc tattgagcag gctgctctgg cagcggccaa ctctgccctg gcgaatgctg 120tggtagttag gccctttctc tctcaccagc agattgagat cctcattaac ctaatgcaac 180ctcgccagct tgttttccgc cccgaggttt tctggaacca ccccatccag cgtgttatcc 240acaatgagtt ggagc 255 30 226 DNA Hepatitis E virus Pakistan SAR55(M80581)30 gaggcccatc agtttatcaa ggctcctggc atcactactg ctattgagca ggctgctcta 60gcagcggcca actctgccct tgcgaatgct gtggtagtta ggccttttct ctctcaccag 120cagattgaga tccttattaa cctaatgcaa cctcgccagc ttgttttccg ccccgaggtt 180ttctggaacc atcccatcca gcgtgttatc cataatgagc tggagc 226 31 232 DNAHepatitis E virus Mexico(M74506) 31 gccatggagg cccaccagtt cattaaggctcctggcatca ctactgctat tgagcaagca 60 gctctagcag cggccaactc cgcccttgcgaatgctgtgg tggtccggcc tttcctttcc 120 catcagcagg ttgagatcct tataaatctcatgcaacctc ggcagctggt gtttcgtcct 180 gaggtttttt ggaatcaccc gattcaacgtgttatacata atgagcttga gc 232 32 20 DNA Hepatitis E virus 32 gcagaccacrtatgtgktcg 20 33 20 DNA Hepatitis E virus 33 ccacrtatgt ggtcgaygcc 20 3420 DNA Hepatitis E virus 34 acmarctgsc grggytgcat 20 35 20 DNA HepatitisE virus 35 cgytgratwg grtgrttcca 20 36 19 DNA Hepatitis E virus 36tgktcgaygc catggaggc 19 37 19 DNA Hepatitis E virus 37 tgktcgaygccatggaggc 19 38 20 DNA Hepatitis E virus 38 aygccatgga ggcccaycag 20 3920 DNA Hepatitis E virus 39 ckracyacca cagcattcgc 20 40 20 DNA HepatitisE virus 40 ggcckracya ccacagcatt 20 41 53 DNA Hepatitis E virus 41aaggctcctg gcrtyactac tgcyatwgag caggcwgctc trgcwgcggc caa 53 42 19 DNAHepatitis E virus 42 ctcctggcat cactactgc 19 43 19 DNA Hepatitis E virus43 ctcctggcat tactactgc 19 44 7256 DNA Hepatitis E Virus JapanJKN-Sap(AB074918) 44 gcagaccacg tatgtggtcg atgccatgga ggcccatcagttcattaagg ctcctggcat 60 tactactgcc attgagcagg ctgctctggc tgcggccaattccgccttgg cgaatgctgt 120 ggtggtccgg ccgttcttat ctcgtgtaca aactgagattcttattaatt tgatgcaacc 180 ccggcagttg gttttccgcc ctgaggtgct ctggaatcaccctatccagc gggttataca 240 taatgaattg gaacagtact gccgggcccg ggccggccgttgcctggagg ttggggctca 300 cccgaggtcc attaatgaca atcccaatgt cctgcacaggtgctttctta gaccggttgg 360 ccgagacgtc cagcgctggt actctgcccc cacccgtggccctgcggcca actgccgccg 420 ctccgcgttg cgtggtctcc ctcccgctga ccgcacttattgctttgatg gattctcccg 480 ctgtgctttt gctgcagaga ccggcgtggc cctttactctctgcatgacc tttggccagc 540 tgatgtcgca gaggctatgg cccgccacgg gatgacacgcctatatgctg cactacacct 600 ccctcctgag gtgctgttgc cacccggcac ttaccacacaacctcgtatc tcctgatcca 660 cgacggcgac cgtgccgtcg taacttatga gggcgatactagtgcaggct acaatcacga 720 tgtttccata cttcgtgcgt ggatccgtac tactaaaatagttggtgacc acccgttggt 780 tatagagcgt gtgcgggcca ttggatgtca ttttgtgctgctgctcaccg cagcccctga 840 gccgtcacct atgccttatg tcccctaccc tcgttcaactgaggtgtatg tacgatctat 900 atttggccct ggtggctccc catctttgtt cccgtcagcctgctctacta aatctacttt 960 tcatgctgtc ccggttcata tctgggaccg gcttatgctttttggtgcca ccctggacga 1020 tcaggcgttt tgttgttcac ggctcatgac ttacctccgtggtattagct acaaggtcac 1080 tgtcggtgcg cttgttgcta atgagggatg gaatgcctctgaggacgccc ttactgcagt 1140 gatcactgcg gcttacctga ctatttgcca ccaacgctaccttcgaaccc aggcgatatc 1200 caagggtatg cgccggttgg aggttgagca tgcccagaaattcatcacaa ggctctacag 1260 ctggctattt gagaaatctg gtcgtgatta tatccccggccgccagcttc agttctatgc 1320 acaatgtcgg cggtggttat ctgcaggctt ccacctcgaccccagggtgc ttgtcttcga 1380 tgaagcagtg ccatgccgct gtaggacgtt tttgaagaaggtcgcgggta aattctgctg 1440 ttttatgcgg tggctagggc aggagtgcac ctgtttcttggagccagctg agggcctaat 1500 tggagaccaa ggccatgata atgaggccta tgagggttctgaggtcgacc cggctgaacc 1560 tgcacatctt gatgtttcgg ggacctatgc tgtccatgggcatcagcttg aggcccttta 1620 tagggcactc aatgtcccac atgatattgc cgctcgagcctcccggctaa cggctactgt 1680 cgagcttgtt gcaagtccag accgcttaga gtgccgtactgtgcttggta ataagacctt 1740 tcggacaacg gtggttgatg gtgcccatct tgaagcaaatggccctgagg agtatgttct 1800 atcattcgac gcctctcgtc agtctatggg ggccggatcgcacagcctca catatgagct 1860 cacccctgct ggtctgcagg tcaggatttc atctaatggcttggattgta ccgccgtatt 1920 ccctcccggc ggcgccccta gcgccgcacc gggggaggtggcagccttct gcagcgccct 1980 ttatagatat aacaggttca cccaacggca ctcgctaaccggtggattat ggttacaccc 2040 tgaggggttg ctgggcatct tccccccttt ctctcctggacacatctggg agtctgctaa 2100 cccattttgt ggggagggga ccttgtatac ccgaacctggtcaacatctg gcttctctag 2160 cgacttctcc ccccctgagg cggccgcccc tgttccggctgctgccccgg ggctgcccca 2220 ccccacccca cctgttagtg acatttgggt gctgccaccaccctcagagg agtcccagat 2280 cgatgcggca cctgtgcccc ctgtccctaa gactgttggattgcctagcc ccattgtact 2340 tgctcctccc tcccctcttc cttcccccgt gcgtaagccaccatcacccc cgccttctcg 2400 cactcgtcgt ctcctctaca cctatcctga cggcgctagggtatatgcgg ggtcgttgtt 2460 tgaatcagac tgtgactggc tagttaacgc ctcaaatccgggccaccgtc ctggaggtgg 2520 cctctgccac gccttttacc aacgcttccc agaggcgttttacccaactg aattcattat 2580 gcgtgagggc cttgcagcat ataccctgac cccgcgccctatcattcatg cagtggctcc 2640 cgactatagg gtcgagcaga atccgaagag gcttgaggcagcgtaccggg aaacttgctc 2700 ccgtcgcggc accgctgcct atccgctttt gggctcgggtatataccagg tccctgttag 2760 tctcagtttt gatgcctggg aacgcaatca tcgccccggcgacgagcttt acttgactga 2820 gcccgctgca gcttggtttg aggctaataa gccatcgcagccggcgctta ctataactga 2880 ggacacggct cgtacggcca atctggcatt agagattgatgccgccacag aggttggccg 2940 tgcttgtgcc ggctgcacta tcagcccggg ggttgtgcattaccagttta ctgccggggt 3000 cccgggctcg ggcaagtcaa ggtccataca acagggagacgtcgatgtgg tggttgtgcc 3060 cacccgggag cttcgtaata gttggcgccg ccggggttttgcggctttca cacctcacac 3120 agcggcccgt gttactattg gtcgccgcgt tgtgattgatgaggctccgt ccctcccgcc 3180 gcacttgctg ctgctacaca tgcaacgggc ctcctcggtccatctcctcg gcgacccaaa 3240 tcagattcct gctattgatt ttgaacatgc cggcctggtccccgcgatcc gtcccgagct 3300 tgcaccaacg agctggtggc atgttacaca ccgctgcccggcagatgtgt gtgagcttat 3360 acgtggggcc taccctaaga tccagaccac gagtcgtgtgctacggtccc tgttttggaa 3420 cgaaccggcc attggccaga agctggtttt cacgcaggctgctaaggctg ctaatcctgg 3480 tgcgatcacg gttcatgagg ctcagggtgc caccttcacggagaccacaa tcatagccac 3540 ggctgatgct aggggcctta ttcagtcatc ccgagctcacgctatagtcg cactcacccg 3600 ccacactgag aagtgtgtta ttttagatgc ccccggcctactgcgcgagg tcggtatttc 3660 agatgtgatt gtcaataact ttttccttgc tggtggagaggttggccacc accgcccctc 3720 cgtgatacct cgcggtaacc ccgatcagaa tctcgggactctacaggcat tcccgccgtc 3780 ttgccagatt agtgcctacc accagttggc tgaggaattaggccaccgcc cagctcctgt 3840 cgccgccgtc ttaccccctt gcccggagct tgagcagggcctgctctaca tgccacaaga 3900 gcttactgtg tccgatagtg tgttggtatt tgaactcacagatatagtcc attgccgtat 3960 ggccgctcca agccagcgaa aggctgttct ctcaacacttgtcgggaggt atggccgtag 4020 aacgaaatta tatgaggcgg cacattcaga tgttcgtgagtccctagcta ggttcatccc 4080 cactatcggg cctgttcagg ccaccacatg tgagttgtatgagttggttg aggccatggt 4140 ggagaagggt caggacggct ctgccgtcct agagcttgacctttgcaatc gtgacgtctc 4200 gcgtatcaca tttttccaaa aggattgcaa taaattcacaactggtgaga ctattgccca 4260 tggcaaggtt ggccagggta tatcggcctg gagtaagaccttctgtgccc tgtttggccc 4320 gtggttccgc gctatagaaa aagagatatt ggccctgctcccgcctaata tcttttatgg 4380 cgacgcttat gaagagtcag tgtttgctgc cgctgtgtctggggcggggt catgtatggt 4440 atttgaaaat gatttttcgg aatttgacag tactcagaacaacttctctc tcggccttga 4500 gtgtgtggtc atggaggagt gcggcatgcc ccagtggttgattaggttgt accatctggt 4560 tcggtcagcc tggattttgc aggcgccgaa ggagtctcttaagggttttt ggaagaagca 4620 ctctggtgag cctggtaccc ttctctggaa caccgtctggaacatggcga ttatagcgca 4680 ctgttacgag ttccgtgact ttcgcgttgc cgccttcaagggtgatgatt cggtggtcct 4740 ttgcagcgac tatcggcaga gccgcaatgc ggctgccttaattgcaggct gtgggctcaa 4800 attgaaggtc gattatcgtc ctattgggct gtatgctggggtggtggtgg cccctggttt 4860 ggggacactg cccgacgtgg tgcgttttgc tggtcggttgtctgaaaaga attggggccc 4920 cggccctgaa cgtgctgagc agctgcgtct cgctgtttgtgatttccttc gagggttgac 4980 gaatgttgcg caggtttgtg ttgatgttgt gtcccgtgtttacggagtca gccccgggct 5040 ggtacataac cttattggca tgctgcagac cattgccgatggcaaggctc acttcacaga 5100 gaccattaaa cctgtgcttg accttacgaa ttccatcatacagcgggaag aatgaataac 5160 atgtcttttg catcgcccat gggatcacca tgcgccctagggctgttctg ttgttgttcc 5220 tcgtgctttt gcctatgctg cccgcgccac cggccggtcagccgtctggc cgtcgccgtg 5280 ggcggcgcag cggcggtgcc ggcggtggtt tctggggtgacagggttgat tctcagccct 5340 tcgccctccc ctatattcat ccaaccaacc ccttcgccgccgatgtcgtt tcacaacccg 5400 gggctggaac tcgccctcga cagccgcccc gcccccttggctccgcttgg cgtgaccagt 5460 cccagcgccc ctccgctgcc ccccgccgtc gatctgccccagctggggct gcgccgttga 5520 ccgctgtatc accggctcct gacacagccc ctgtgcctgatgttgattca cgcggtgcta 5580 tcctgcgccg gcagtacaat ctgtccacgt ccccgctcacgtcatctgtc gcctcgggca 5640 caaatctggt tctctatgct gccccgctta atcctctcctgccccttcag gatggcacca 5700 acactcatat tatggccact gaggcatcca attatgcccagtatcgggtt gttcgagcta 5760 cgatccgtta tcgcccgttg gtgccgaatg cagttggcggttatgctatt tctatttctt 5820 tttggcctca aaccacaact actcccacct ctgtcgacatgaattctatc acttccactg 5880 atgttaggat tttggttcag cccggcattg cctccgagttagtcatccct agtgagcgcc 5940 tccactaccg caatcaaggc tggcgctctg ttgagaccacgggtgtggcc gaggaggagg 6000 ctacttccgg tctggtaatg ctttgtattc atggctctcctgttaattcc tacactaata 6060 caccttatac tggtgcactg gggctccttg attttgcattagagcttgaa tttagaaatc 6120 tgacacccgg gaacacaaac acccgtgttt cccggtataccagcacagcc cgtcaccggc 6180 tgcgccgcgg tgctgatggg actgctgagc ttaccaccacagcagccaca cgtttcatga 6240 aggatttaca ttttactggc acgaatggtg ttggtgaggtgggtcgtggc atcgctctga 6300 cattgtttaa tctcgctgac acgcttctcg gtggtttaccgacagaattg atttcgtcgg 6360 ccgggggtca actgttttac tcccgccctg ttgtctcggccaatggcgag ccaacagtaa 6420 agttatacac atctgttgag aatgcgcagc aagataagggcattaccatc ccacacgata 6480 tagatctggg tgactcccgt gtggttattc aggattatgataaccagcac gagcaagatc 6540 ggcctactcc gtcacctgcc ccctcccgcc ctttctcagttcttcgtgct aatgatgttc 6600 tgtggctctc cctcaccgcc gctgagtatg accagactacgtatgggtcg tccaccaacc 6660 ctatgtatgt ctccgacaca gtcacgctcg ttaatgtggccactggagcc caggctgtgg 6720 cccgctctct tgattggtct aaagttacct tggatggccgcccccttact accattcagc 6780 agtattctaa gacattctat gtccttccgc tccgcgggaagctgtctttc tgggaggctg 6840 gtacgactaa ggccggttac ccgtataatt ataatactactgctagtgat cagatcttga 6900 ttgagaacgc ggccggccac cgtgtcgcta tttctacctatactactagc ttgggtgccg 6960 gccctacctc gatctctgcg gtcggtgtac tagctccacattcggccctc gccgttctag 7020 aggacaccgt tgattacccc gcccgcgctc acacttttgatgatttctgc ccggagtgcc 7080 gtaccctcgg tttgcagggt tgtgcattcc agtctactatcgctgagctt cagcgtctta 7140 aaatgaaggt aggtaaaacc cgggagtctt aattaattccttttgtgccc ccttcgcagc 7200 tttctctggc tttatttctt atttctgctt ttcgcgctccctggaaaaaa aaaaaa 7256 45 7233 DNA Hepatitis E Virus JapanJMY-Haw(AB074920) 45 ccatggaggc ccatcaattc attaaggctc ctggcattactactgccatt gagcaggctg 60 ctctggctgc ggccaattcc gccttggcga atgctgtggtggtccggccg tttttatctc 120 gtgtacaaac cgagattctt attaatttga tgcaaccccggcagttggtt ttccgtcctg 180 aggtgctctg gaatcatcct attcagcggg ttatacataatgaattggaa cagtactgcc 240 gggcccgggc cggccgctgc ctggaggttg gggcccacccgagatccatt aatgataatc 300 ccaatgtcct gcacaggtgc tttcttagac cggtcggccgagatgtccaa cgctggtact 360 ctgcccccac ccgcggtcct gcggccaatt gccgccgctccgcgttgcgt ggtctccctc 420 ccgctgaccg cacttattgc tttgatggat tctcccgctgtgcttttgct gcagagaccg 480 gcgtggctct ttactctttg catgaccttt ggccagctgatgttgcagag gctatggccc 540 gccatgggat gacacgccta tatgctgtac tacaccttcctcctgaggtg ctgctaccac 600 ccggcactta ccacacaact tcgtatctcc tgatccacgacggcgaccgt gccgttgtaa 660 cttatgaggg tgatactagt gcgggctaca accacgatgtttccatactt cgtgcgtgga 720 tccgcactac taaaatagtt ggtgaccacc cgctggttatagagcgtgtg cgggccattg 780 gatgtcactt tgtgctgctg ctcaccgcag cccctgagccgtcacctatg ccttatgtcc 840 cctaccctcg ttcaactgag gtgtatgtac gatctatatttggccctggt ggctccccat 900 ctctgttccc gtcagcctgc tctactaaat ctacttttcatgctgtcccg gttcatatct 960 gggatcggct tatgcttttt ggtgccaccc tggacgatcaggcgttttgt tgttcacggc 1020 tcatgactta cctccgtggt attagctaca aggtcactgtcggcgcgctg gtcgctaatg 1080 aaggatggaa cgcctctgag gacgccctta ctgcagtgatcactgcggct tatctgacta 1140 tttgccacca gcgctacctc cgaacccagg cgatatccaagggtatgcgc cggttggagg 1200 ttgagcatgc ccagaaattt attacaaggc tctacagctggctatttgag aaatctggcc 1260 gtgattatat tcccggccgc cagcttcagt tctatgcacaatgccggcgg tggctatctg 1320 caggtttcca tctcgacccc agggtgcttg tctttgatgaatcagtgcca tgccgttgta 1380 ggacgttttt gaagaaggtc gcgggtaaat tctgctgttttatgcggtgg ctggggcagg 1440 agtgcacctg ttttttggag cccgccgagg gtttagttggagaccaaggc catgacaacg 1500 aggcctatga gggttctgag gtcgacccgg ccgaacctgcacatcttgat gtttcgggta 1560 cctatgctgt ccatgggcac cagcttgagg ccctttatagagcacttaat gtcccacatg 1620 atattgccgc tcgagcctcc cggctaacgg ctactgtcgagcttgttgca agtccagacc 1680 gcttggagtg ccgtactgtg ctcggtaata agaccttccggacaacggtg gttgatggcg 1740 cccatcttga agcaaatggc cctgagcagt atgttctatcatttgacgcc tcccgtcagt 1800 ctatgggggc cgggtcgcat agcctcactt atgagctcacccctgccggt ctgcaggtca 1860 ggatttcatc taatggcctg gattgcaccg ctgtattccctcccggcggc gcccctagcg 1920 ccgcaccggg ggaggtggca gccttctgca gcgccctttatagatataac aggttcaccc 1980 aacggcactc gctgactggt ggattatggt tacaccctgaggggttgctg ggtatcttcc 2040 cccctttctc acctgggcac atctgggagt ctgctaatccattttgtggg gaggggacct 2100 tgtatacccg aacctggtca acatctggct tttctagtgacttctccccc cctgaggcgg 2160 ccgcccctgt tccggctgct gccccgggat tgccccaccctactccacct gttagtgata 2220 tttgggtgct gccacccccc tcagaggggt cccagatcgatgcggcacct gtgccccctg 2280 ttcctaagac tgttggattg cctagcccca ttgtacttgctcctcccccc ccctttcctt 2340 cccccgtgcg taagccatca tcacccccgc cttctcgcacccgtcgtctc ctctacacct 2400 atcctgacgg cgctagggta tatgcggggt cattgtttgaatcagattgt gactggctgg 2460 ttaatgcctc aaacccggga caccgtcctg gaggtggcctttgccatgcc ttttaccagc 2520 gtttcccaga ggcgttttac ccgactgaat tcattatgcgtgagggcctc gcagcatata 2580 ccctgacccc gcgccctatc attcatgcag tggctcccgactatagggtt gagcagaacc 2640 cgaagaggct tgaggcagcg tatcgggaaa cttgctctcgtcgtggcacc gctgcctatc 2700 cgcttttggg ctcgggtata taccaggtcc ctgttagtctcagttttgat gcctgggaac 2760 gcaatcatcg ccccggcgac gagctttatc tgactgagcccgctgcagcc tggtttgagg 2820 ctaataagcc ctcgcagccg gcgcttacta taactgaggacacggctcgt acggccaacc 2880 tggcattaga gattgatgcc gccacagagg ttggccgtgcttgtgccggc tgcactatta 2940 gcccagggat tgtgcattat cagtttactg ccggggtcccgggctcgggc aagtcaaggt 3000 ccatacaaca gggagacgtc gatgtggtgg ttgtgcccacccgggagctt cgtaatagtt 3060 ggcgtcgccg gggttttgcg gctttcacgc ctcacacagcggcccgtgtt actatcggtc 3120 gccgcgttgt gattgatgag gccccatccc tcccgccgcatctgctgctg ttacacatgc 3180 aacgggcctc ctcggtccat ctcctcggcg acccaaatcagattcctgct attgattttg 3240 agcatgccgg cttggtcccc gcgatccgcc ccgagcttgcgccaacgagc tggtggcacg 3300 ttacacaccg ctgcccggca gacgtgtgcg agcttatacgtggagcctac cctaagatcc 3360 agaccacgag ccgtgtgcta cggtctctgt tttggaacgaaccggccatt ggccagaagc 3420 tggttttcac gcaggctgct aaggctgcta atcctggtgcgatcacggtt catgaagctc 3480 agggtgccac cttcacggag accacaatta tagccacggctgacgccagg ggccttattc 3540 agtcatcccg ggctcacgct atagttgcac tcactcgccacactgagaag tgtgttattt 3600 tagatgcccc cggcctgttg cgcgaggtcg gtatttcggatgtgattgtt aacaactttt 3660 tccttgctgg tggagaggtc ggccaccacc gcccctctgtgataccccgc ggcaaccccg 3720 atcagaatct cgggacttta caggcattcc cgccgtcttgccagattagt gcctaccacc 3780 agttggctga ggaattaggc caccgcccgg cccctgtcgctgccgtctta cccccttgcc 3840 cggagcttga gcagggccta ctctacatgc cacaagagcttactgtgtcc gatagtgtgt 3900 tggtttttga gctcacagat atagtccact gtcgtatggccgccccaagt cagcgaaagg 3960 ctgttctctc tacacttgtg gggaggtatg gccgtagaacgaaattatat gaggcggcgc 4020 attcagatgt tcgtgagtcc ttagctaggt tcatccccactatcgggcct gttcaggcca 4080 ccacatgtga gttgtatgag ttggtcgagg ccatggtggagaagggtcag gacggctctg 4140 ccgtcctaga gcttgatctt tgcaatcgtg acgtctcgcgtatcacattt ttccaaaagg 4200 attgcaataa gtttacaact ggtgagacta tagcccatggcaaggttggc cagggtatat 4260 cggcctggag caagaccttc tgcgccctgt tcggcccgtggttccgcgct atagaaaaag 4320 aaatattggc cctgctcccg cctaatattt tttatggcgacgcttatgag gagtcagtgt 4380 ttgctgccgc tgtgtctggg gcggggtcat gtatggtatttgaaaatgat ttctcggagt 4440 ttgacagtac tcagaataat ttctctctcg gtcttgagtgtgtggtcatg gaggagtgcg 4500 gcatgcccca atggttgatt aggttgtacc atctggttcggtcagcctgg attttgcagg 4560 cgccgaagga gtcccttaag ggtttttgga agaagcactctggtgagccc ggcacccttc 4620 tctggaatac cgtctggaac atggcgatta tagcgcattgttacgagttc cgtgactttc 4680 gcgttgccgc cttcaagggt gatgattcgg tggtgctttgtagcgactac cggcagagcc 4740 gcaatgcggc tgccttaatt gcaggctgtg ggctcaaattgaaggtcgat taccgcccta 4800 ttgggctgta cgctggggtg gtggtggccc ctggtttagggacactgcct gatgtggtgc 4860 gttttgctgg tcggttgtct gaaaagaatt ggggccccggccctgaacgc gctgagcagc 4920 tgcgtctcgc cgtttgtgat ttccttcgag ggttgacgaatgtcgcgcag gtctgtgttg 4980 atgttgtgtc ccgtgtctac ggagtcagcc ccgggctggtacataacctt attggcatgc 5040 tgcagactat cgccgatggc aaggcccact ttacagagaccattaaacct gtgcttgacc 5100 ttacgaattc catcatacag cgggaggaat gaataacatgtcttttgcac cgcccatggg 5160 atcaccatgc gccctagggc tgttctgttg ttgttcctcgtgcttctgcc tatgctgccc 5220 gcgccaccgg ccggccagcc gtctggccgt cgtcgtgggcggcgcagcgg cggtaccggc 5280 ggtggtttct ggggtgacag ggttgattct cagcccttcgccctccccta tattcatcca 5340 accaacccct tcgccgccga tgtcgtttca caacccggggctggagctcg ccctcgacag 5400 ccgccccgcc cccttggctc cgcttggcgt gaccagtcccagcgcccctc cgctgccccc 5460 cgccgtcgat ctgccccagc tggggctgcg ccgttgaccgctgtatcacc ggctcctgac 5520 acagcccctg tacctgatgt tgattcacgc ggcgctattctgcgccggca gtacaatttg 5580 tccacgtccc cgcttacgtc atccgttgcc tcgggtacaaatctggttct ttatgctgcc 5640 ccgcttaatc ctctccttcc ccttcaggat ggcaccaacactcatattat ggccactgag 5700 gcatctaatt atgcccagta tcgggttgtt cgagctacgatccgttatcg cccgttggtg 5760 ccgaacgctg ttggcggtta tgctatttct atctctttttggcctcaaac cacaactact 5820 ccaacttctg ttgatatgaa ttccattact tccactgatgttaggatttt ggttcagccc 5880 ggtattgcct ccgagttagt catccctagt gagcgcctccactaccgcaa tcaaggctgg 5940 cgctctgttg agaccacggg tgtggccgag gaggaggctacttccggtct ggtaatgctt 6000 tgcattcatg gttctcctgt taattcctat actaatacaccttatactgg tgcactgggg 6060 ctccttgatt ttgcattaga gcttgaattt agaaatctgacacccgggaa cacaaacacc 6120 cgtgtttccc ggtataccag cacagcccgt caccggctgcgacgcggtgc tgatgggact 6180 gctgagctca ccaccacagc agccacacgt tttatgaaggatttgcattt tactggcacg 6240 aacggtgttg gtgaggtggg tcgtggcatc gctctgacattgtttaatct cgctgatacg 6300 cttctcggtg gtttaccgac agaattgatt tcgtcggccgggggtcagct gttttactcc 6360 cgccctgttg tctcagccaa tggcgagcca acagtaaagttatatacatc tgttgagaac 6420 gcgcagcaag ataagggcat taccatccca cacgatatagatttgggtga ctcccgtgtg 6480 gttatccagg attatgataa ccagcacgag caagatcggcctaccccgtc acctgccccc 6540 tcccgccctt tctcagttct tcgtgccaat gatgttctgtggctctccct caccgccgct 6600 gagtacgacc agactacata tgggtcgtcc accaaccctatgtatgtctc cgacacggtc 6660 acgctcgtta atgtggccac tggtgctcag gctgttgcccgctctctcga ttggtctaaa 6720 gttaccttgg atggccgccc ccttactact attcagcagtattctaagac attctatgtc 6780 ctcccgcttc gcgggaagct gtctttttgg gaggctggcactaccaaggc cggctacccg 6840 tataattata atactactgc tagtgatcaa attttgattgagaacgcggc cggccaccgt 6900 gtcgctattt ctacctatac tactagtttg ggtgccggtcctacctcgat ctctgcggtc 6960 ggtgttctag ccccacactc ggccctcgcc gctctagaggacaccgttga ttaccccgcc 7020 cgcgctcaca cttttgatga tttttgcccg gagtgccgtaccctcggttt gcagggttgt 7080 gcattccagt ctactatcgc tgagcttcag cgtcttaaaatgaaggtagg taaaacccgg 7140 gagtcttaat taattccttt tgtgccccct tcgtagttccctctggcttt atttcttatt 7200 tctgctcccc gcgctccctg gaaaaaaaaa aaa 7233 467229 DNA Hepatitis E Virus Japan JAK-Sai(AB074915) 46 ccatggaggcccatcagttt ataaaggctc ctggcgtcac tactgctatt gagcaggcag 60 ctctagcagcggccaactcc gccttggcga atgctgtggt ggttcggcct ttcttatccc 120 ggctacagacagagatactc attaacctga tgcagccccg gcagcttgtt ttccggcctg 180 aggttttatggaatcaccca attcagcgtg tgatccacaa tgagctcgaa cagtattgtc 240 gggctcgcgctggccgctgc cttgaagtgg gcgctcatcc gcgctccatt aacgacaatc 300 ccaatgttcttcaccgctgc tttttaaaac ctgttggccg cgatgttcag cggtggtaca 360 ccgcccctacccgtggccct gcagcgaact gtcgccgatc ggcccttcgt ggccttccac 420 ctgccgaccggacgtattgc tttgatggtt tctccggctg tacattcgct gctgagacgg 480 gcgtagccctctactcactg cacgatctct ggcccgccga tgtcgctgag gcgatggctc 540 gccacggcatgactcggttg tatgcagccc tccacctccc cccggaggtg ctactccccc 600 ccggcacctatcatactacc tcgtatctcc tcatccatga tggggaccgt gcagtgatta 660 cttatgagggggactctagc gctgggtaca accatgatgt atccatcctg cgcgcctgga 720 tccgcactaccaaggtcact ggtgaccacc cgttggtaat tgagcgggtt cgggcggtgg 780 gttgtcactttgtgctcctc ctcacagccg cgcctgaacc atcaccaatg ccctatgttc 840 catatcctcgttctaccgag gtttatgtgc ggtccatttt tggccctggc ggttcacctt 900 ccctgttcccatctgcctgc tctactaagt caacatttca tgctgtccct gtgcatatat 960 gggacagactcatgctcttt ggtgcgaccc tcgacgacca ggccttctgt tgctcgcggc 1020 taatgacatacctccgtggc attagttaca aggttacggt cggtgctctc gtcgccaatg 1080 agggttggaatgcctccgaa gatgcattga ctgccgtgat tactgcggcc tatctcacca 1140 tttgccaccagaggtatctc cgcacgcagg ctatctcgaa agggatgaaa agattggagc 1200 ttgagcatgcacagaagttt ataacacgcc tttacagctg gctgtttgaa aagtccggcc 1260 gtgactacatccccggccgt caactgcagt tctacgctca gtgccgtcgg tggctatctg 1320 ctggtttccaccttgatcct cgtgtgctcg tctttgacga agcagccccc tgccgctgcc 1380 gtagccttctccgtaaagca gcacataaat tttgctgctt tatgcggtgg ctggggcagg 1440 actgtacctgtttcctccag cccatcgaag gaagggttgg tgagcagggt tatgacaatg 1500 aggcatttgaggggtcggac gtcgatcctg ctgaggaggc tactgtgagc atttctgggt 1560 catatatcgtcactggcagc cagctgcagc ccctctacca ggcgcttggc atcccttctg 1620 atcttgccgcccgagcgggt cggcttactg ccaccgtcga agtctctgat gccgacggcc 1680 gccttacttgtaagaccatc atgggcaata agacttttac aacagttttt actgatggtg 1740 cccagctagaggtcaacggg ccagagcaat atgtgctgtc gtttgatttg gctaaacaga 1800 cgatggccgctggcccgcat agccttagtt atgttctgac atccgcgggc cttgaggtgc 1860 gtgttgtttctgctgggctt gactgtaagg ctgtttttcc atctggggtt gcaaccccct 1920 ccgcttctggcgaggtgtca gccttctgtt cagctttata caggtttaac cgttgcgttc 1980 agcggcattctcttattggg ggcttgtggt attaccctga ggggctaatc ggcctgttcc 2040 caccgtttgctcccggccac acctgggagt caaccaaccc tttctgtgga gaaagtaccc 2100 tttatactcgcacctggtcg gtgtcagggt tttctagctg tttctcccca cttgagcccc 2160 ctgcctcgggttcactaccc cctgcggaga tcgacccacc cgtgactgtt gatgccccat 2220 ctccatctattttggcattg ccccggccct cagtttttga acagaccacg cccccattgg 2280 atccagctggtgacgctgct gcttcggccc cgccaggtgc ccctggtgtg cccccggcac 2340 cagcgcggcctgtaacccac ccatccgggc cccgccggcg gttactccat acttatcctg 2400 atggctcaaaggtgtatgcc ggttctctct ttgagtccga gtgtacttgg ctggttaatg 2460 catccaatcccggtcaccgc cctggtggcg gtctctgcca tgcgttttac cagcggtttc 2520 cggagtcatttgatcccgcc gagtttgtca tgtctgatgg gtttgcggcc tacaccttga 2580 caccccggcccataattcac gctgttgctc ccgattatcg agtagaacat aatcctaaga 2640 ggctcgaggctgcctatcgg gagacgtgct ctcgccgcgg gacggccgct taccctctgc 2700 tcggcgccggtatatataag gtacctgttg ggctgagttt tgatgcctgg gaacgtaacc 2760 accggcccggggatgagttg tacctgaccg agccagctat agcttggttt gaggctaacc 2820 ggcctactctccctgcgctt accattactg aggacacggc acgaacagca aatctggcgc 2880 tggagttggattcggccact gaggttggcc gggcatgtgc cggctgtcgt gttgagcctg 2940 gtgtcgtccactaccagttt acggcaggtg tccctggctc cggcaagtca cggtcaattc 3000 agcagggtgaggtcgatgtg gtggtggtgc caactcgtga gctgcgtaac tcctggcgac 3060 gccgtgggtttgcagcttac acaccccaca ccgcggcccg cgtcacccgc ggtcgcagga 3120 ttgttattgacgaggccccg gcacttccac cacatttact tctgctacat atgcagcggg 3180 cctcgtcagtccacctcctc ggcgacccca accagatccc tgctattgac ttcgagcatg 3240 ccggtcttgtcccggcaatc cggcctgagc ttgtcccaac aaagtggtgg catcttaccc 3300 ataggtgcccagcagacgtc tgtgagctaa ttcgtggcgc gtatccaaag atccagacgg 3360 caagccgtgtcctccgctct ctgttttggg gagagccccc tgtaggccaa aagttagtat 3420 tcactcaggcggcaaaggcc gctaaccctg gtgcaattac agtccatgag gcccagggtg 3480 ccacatttactgagaccact attattgcta cggcagacgc ccgcgggctg atccagtctt 3540 ctagggcccacgctattgta gccctgactc gccacacaga gaaatgtgta gttgttgatg 3600 ccccggggctccttcgtgag gttggtattt ctgatgctat tgttaataac tttttccttt 3660 ccggcggccagattggtcaa caccgcccat cagttatacc gcgcggcact gttgacagca 3720 atgttgatacgctcgatgcg tttccacctt cctgtcaatt tagcgcctac catcagcttg 3780 cggaggaactcggtcatcga ccggctccga tcgctgccgt tttgcccccc tgcccagagc 3840 tcgaacagggtctgctttat atgccccagg aactaactac gtccgacagc gtgcttacat 3900 ttgaattaacagatatagtg cactgccgta tggcggctcc aagccagcgc aaggcagtcc 3960 tgtcgacccttgtcggcagg tatggccgtc gtacgaagtt gtatgaggcc gcccatgcgg 4020 acgttcgcggatccctgaac cactttatcc ccgagctcgg ccccattagt gttaccacct 4080 gtgagctttacgagcttgtg gaggctatgg tagagaaggg gcaggatggc tctgcggtct 4140 tggagcttgatctatgtagc cgtgatgtgt cgcgtataac attctttcag aaggattgta 4200 ataaatttacgacaggagag acaatagcac acggcaaagt tgggcagggg atatctgcgt 4260 ggagcaaaacgttttgtgcc ctatttggcc cttggttccg tgccattgag aaggagattc 4320 ttgcagcacttgctcccaat gttttctatg gtgatgcata tgaagacaca gtcctggccg 4380 ctgctgttgctggggctcct ggctgcaagg tttttgagaa tgatttttct gagtttgata 4440 gcactcaaaataacttctca cttggtttgg agtgtataat catggaggag tgcggcatgc 4500 cgcaatggatgatccgactt taccatcttg tccgctctgc ctgggtcctg caagccccaa 4560 aggagtccctgcggggtttc tggaagaagc actcaggcga gcctggcacc ttgctttgga 4620 acacggtctggaacatggcg gtaatagcac actgttacga gttccgcgac ttgaaagtcg 4680 cggcgtttaaaggggatgac tctgttgtgc tctgtagtga ctaccggcag agccgcaatg 4740 cggccgccttaatcactggt tgtgggctga agcttaaggt ggattttagg cccatcgggc 4800 tgtatgctggtgttgttgtg gccccgggtc tcgggaccct tcctgatgtt gttaggttcg 4860 ctgggcggctctcagagaaa aactgggggc cgggtccaga gagggctgag cagctacggc 4920 tggcagtttgtgatttcctg cgaaagttaa cgaatgtggc tcaagtctgt gtggatgttg 4980 tttcgcgggtttatggtgtt agccccggct tagtacataa cctgattggg atgctccaga 5040 ctatcgccgatggcaaggcg cattttactg aaactgttaa acctgttttg gatctcacca 5100 attccattatacatcgggtg gaatgaataa catgttcttt tgctctgtgc atggagatgc 5160 caccatgcgctctcgggctc ttctgtttct gctcttcgtg tttttgccta tgctgcccgc 5220 gccaccggccggtcagccgt ctggccgtcg ccgcgggcgg cgcagcggcg gtgccggcgg 5280 tggtttctggggtgaccggg ttgattctca gcccttcgcc ctcccctata ttcatccaac 5340 caaccccttcgcatctgaca ttccaaccgc agccggggct ggagctcgcc ctcggcaacc 5400 ggcccgtccactcggctccg cttggcgtga ccaatcccag cgccccaccg cttccgcccg 5460 tcgtcgacctgccccagctg gggctgcgcc gttgactgct gtggccccgg ctcctgatac 5520 cgctcctgtccccgatgttg attctcgcgg cgcaatatta cgccgccaat ataatttatc 5580 tacatccccgcttacatcta ctattgctac tggcactaac cttgttttat atgctgcccc 5640 gttgagccctctgctcccgc tccaagacgg aactaatact catattatgg ctactgaagc 5700 atcaaactacgcccagtatc gcgttgtccg cgccactatt cggtaccgtc cactcgtgcc 5760 gaatgccgttggcgggtacg ctatatctat ttctttctgg cctcagacga caactactcc 5820 gacatctgtcgatatgaatt ccatcacttc caccgatgtt cggattcttg tccagcctgg 5880 tattgcctctgaacttgtga tccctagcga gcgcctgcat taccgtaatc aaggctggcg 5940 ttcggttgagacctctggtg tcgcagagga ggaggcaacc tccggccttg ttatgctttg 6000 cattcatggatcgcctgtga attcttatac taatacaccc tatactggtg cccttggttt 6060 gctcgattttgcactcgagc ttgagttccg caatttgaca cctggtaata caaatacgcg 6120 cgtttcccgatactcgagca gcgcgcgcca caagcttcgc cgcgggcccg acggcactgc 6180 tgaattgactaccactgctg ctacacgctt tatgaaagac cttcacttta cagggactaa 6240 tggtgttggtgaggttggtc gtggtatagc gctaactctg tttaatcttg ctgatacgct 6300 tcttggcgggcttccgacag aattaatttc gtcggctggt ggccagttgt tttactcccg 6360 ccccgtcgtctcagccaatg gcgagccgac tgtgaaactt tacacctcag tcgagaatgc 6420 tcagcaggacaagggtatag ctattccaca tgatattgat cttggcgagt cccgagttgt 6480 tatccaggactatgacaacc aacatgagca agaccgtcct actccctctc cagctccctc 6540 ccgtcctttttctgtccttc gtgctaatga tgtgctttgg ctttcactta cagctgctga 6600 gtatgatcagactacttatg gctcttctac taaccctatg tatgtctctg ataccgtgac 6660 atttgtcaatgtggctactg gcgcccaggg ggtttcccgc tccttggact ggtctaaagt 6720 taccctcgatgggcgcccgc ttactactat tcagcagtac tctaagacct tctttgtcct 6780 accccttcgcggtaagcttt ccttctggga ggctggtact actaaggctg gctatccgta 6840 caattataataccactgcta gtgaccagat cctaattgag aatgcggccg gtcatcgtgt 6900 ttgtatttcaacttatacta ctaatcttgg ctctggccct gtttctatct ctgctgttgg 6960 tgtcctcgcacctcattctg cgctggccgc tctagaggac actgttgatt atcccgctcg 7020 tgctcatacttttgacgatt tctgccctga gtgccgtacg ctcggccttc agggctgtgc 7080 ttttcagtcaactgtcgctg agctacagcg tcttaaaatg aaggtgggta aaacccggga 7140 gtattgatttattttgcttg tgccttcctt ctgttttgtt tcttttattt ctttcttctg 7200 cgcttcgcgctccctggaaa aaaaaaaaa 7229 47 7228 DNA Hepatitis E Virus JapanJKK-Sap(AB074917) 47 ccatggaggc ccaccagttc ataaaggctc ctggcgtcactactgctatt gagcaggcag 60 ctctagcagc ggccaactcc gccttggcga atgctgtggtggttcggcct ttcctatccc 120 ggctacagac agagatactt attaacctga tgcagccccggcagcttgtt ttccggcctg 180 aagtcttgtg gaaccaccca attcagcgcg tgatccacaacgagcttgag cagtactgcc 240 gggctcgggc tggccgctgc cttgaggtgg gtgctcacccacgttctatt aatgacaacc 300 ccaatgttct gcaccgctgt ttcttgaaac ctgtcggccgcgatgtccag cggtggtaca 360 ccgcccccac tcgtggcccc gcagcaaatt gccgccggtcggccctccgt ggcctcccac 420 ctgccgatcg aacctactgt tttaatggtt tttccggctgcacgtttgct gctgagacag 480 ggatagccct ttactcactg cacgacctct ggcctgccgatgttgccgag gcaatggctc 540 gccatggtat gacccggctg tatgcagctc tccacctccccccggaggta ctgctccccc 600 ctggcaccta tcataccact tcgtacctcc tcatccatgatggggaccgt gcagtgatta 660 catatgaggg ggactctagt gctggataca accatgatgtgtccattctg cgcgcctgga 720 tccgcactac taaggtcacc ggcgaccacc cgctggtaattgagcgggtc cgggcggtgg 780 gctgtcactt tgtgcttctt ctcacagctg cacctgaaccatcgccaatg ccctatgtcc 840 cataccctcg ttccaccgag gtttatgttc ggtccatttttggccctggt ggttcaccat 900 ccctgtttcc aactgcctgc tctactaagt caacatttcatgccgtccct gtgcatatat 960 gggacaggct tatgctcttc ggtgcgaccc tcgatgaccaggccttttgc tgttcaaggc 1020 taatgacata ccttcgtggt attagttaca aagtcacagttggcgctctt gtcgccaacg 1080 agggctggaa tgcctccgaa gacgcattaa ctgctgtcattactgcggct tatcttacca 1140 tctgccatca gaggtacctc cgcacacagg ctatctcgaaagggatgaaa agattggagc 1200 ttgagcatgc acagaagttt ataacacgtc tttatagctggttgtttgaa aaatctggcc 1260 gtgattacat ccccggccgt cagttgcagt tttacgcccagtgccgtcga tggctatctg 1320 ctggtttcca ccttgatcct cgtgtgctcg tttttgatgaagcggccccc tgccgctgtc 1380 gtagcttgct tcgcaaagct gcccataaat tttgctgctttatgcgatgg ctagggcagg 1440 attgcacctg cttccttcag cctgttgagg ggagggtcggtgaacagggt tatgataacg 1500 aggcatttga ggggtcggat gtcgaccctg ctgaagaggccactgtgagt atctctggct 1560 cgtacattgt caccggcagc cagttgcagc ctctttaccaggcgctcggt attccttctg 1620 accttgccgc ccgagcgggc cggctcactg ctaccgtcgaagtttcagat accgacggcc 1680 gtctcacttg taagaccact atgggcaata agaccttcacaacagttttt accgacggtg 1740 cccagctgga ggctaatggg ccggagcagt atgtgctatcatttgatttg gctaaacaga 1800 ctatggccgc cggcccgcat agccttagtt acgccttgacacctgcgggt cttgaggtgc 1860 gtgttgtttc tgccggactc gactgtaggg ctgttttcccatctggggtt gcaaccccct 1920 ctgcttccgg ggaggtgtcc gccttctgtt cggctttatacaggtttaac cgctgtgtcc 1980 agcggcattc tctcattggt ggcttgtggt attatcctgaggggctaatt ggtttgtttc 2040 caccgttcgc ccctggccac acctgggagt cagccaatcccttctgtggg gagagcaccc 2100 tttatactcg cacctggtcg gtgtcgggct tttctagctgtttttctcca ttcgagcccc 2160 ccgctctgga ctcaccaccc cccgccgagg ctgatacacctatggctgtc gatgttccac 2220 ccccagctac cttgacatta ccacaacctc cggctcctgaacgggcagta cccccgcaag 2280 atcttgccga tggcgatgtc gctcgggcct ctccgggtgtctctgctgca ccccctgtgc 2340 cggcgcaatc cgtgactgat ccacccgtgt cccgccggcggttacttcat acttatcctg 2400 atgggtcaaa agtgtacgct ggctccctct ttgagtctgagtgtacttgg ttggtcaatg 2460 cgtccaatcc cggccaccgt cccggtggtg gcctttgccatgcattttac cagcggttcc 2520 cggagtcatt tgaccccgcc gagttcgtca tgtccgatgggtttgcagct tataccttga 2580 cgccccgacc tattatccat gctgttgctc ccgactatcgggtagaacat aaccccaaga 2640 ggctcgaggc tgcttatcga gagacgtgct cccgccgtggcacggctgct taccccctgc 2700 ttggtgccgg catatataag gtgcctgttg ggcttagttttgatgcctgg gaacgcaacc 2760 atcggcccgg ggatgagttg taccttactg agccggctatagcttggttc gaggctaacc 2820 gacccactct ccccgcgctc actatcactg aggacacggcacgaacagct aatctggcgt 2880 tggagctaga ttcggccact gaggtcggtc gggcgtgtgctggttgccgt gttgagccag 2940 gcgtcgttca ctaccagttc acggcgggtg tccctggttccggcaagtca cggtcaattc 3000 agcagggcga ggtggatgtg gtggtagtac caactcgtgagctgcgtaac tcatggcgac 3060 gccgcgggtt tgcagcctac acaccccaca ctgcggcccgtgttactcgt ggccgtaggg 3120 ttgtcattga tgaggccccg tcacttccac cacatctgctcttgctgcac atgcagcggg 3180 cctcgtcggt ccaccttctt ggcgacccca accaaatccctgccattgat ttcgagcatg 3240 ctggtcttgt acccgcaatc cggcctgagc ttgtaccaacaaagtggtgg catcttaccc 3300 acaggtgccc ggcagatgtt tgtgagctaa ttcgcggcgcgtaccctaag attcagacag 3360 cgagccgtgt ttttcgctcc ctgttttggg gggagccccctgtcggccaa aaattagtgt 3420 tcactcaggc ggcgaaggcc gctaaccctg gtgcgattacggtccatgag gcccagggcg 3480 ctacattcac tgagactact attattgcta cggcggatgctcgcgggctg attcagtcat 3540 ctagggctca cgctatcgtg gccctaaccc gtcatacggagaaatgtgtg gtcgttgatg 3600 ccccgggact ccttcgtgag gtcggtatct ctgacgccattgttaataac tttttccttt 3660 ctggtggcca gattggtcag caccgtccat cagtcataccgcgtggcact atcaacaaca 3720 atgttgatac gcttgatgca ttcccaccct cttgccagttcagcgcttac caccagcttg 3780 cggaagagct cggccatcga ccggccccga tcgctgccgttctgcccccc tgtcctgaac 3840 ttgaacaggg tctactttac atgcctcagg aattgaccacgtctgatagt gtgcttacgt 3900 ttgaattgac agatatagtg cactgtcgta tggcggcacctagtcagcgt aaggcggtcc 3960 tgtcgactct tgtcggcagg tacggccgcc gtacgaagttgtatgaggct gcccatgcag 4020 atgtccgtgg gtctctaaac cattttatcc ctgagctcggccctgttagt gttaccactt 4080 gtgaacttta cgagcttgtg gaggccatgg tggagaaaggccaggatggt tctgcggttc 4140 tggagctcga tttatgtagc cgtgatgtgt ctcgtataacattcttccag aaggattgta 4200 ataagtttac aacgggcgag acaatagcac atggcaaagttggccagggg atatctgcat 4260 ggagtaaaac cttttgtgct ttgttcggcc catggttccgcgccattgag aaggagatcc 4320 ttgctgtact tgctcccaat gtattctatg gtgatgcatacgaagataca gttctggccg 4380 ccgcagtcgc cggagcccct ggttgcaagg ttttcgagaatgatttctca gagtttgata 4440 gcactcaaaa taatttttca cttgggctgg agtgtataatcatggaggag tgcggcatgc 4500 cgcagtggat gatccggctt tatcaccttg ttcgctctgcttgggttttg caagctccaa 4560 aggagtctct gcgggggttc tggaagaagc actcaggcgagcctggcacc ttgctttgga 4620 atactgtctg gaacatggcg gtcatagccc attgttatgagttccgcgac ttaaaagtcg 4680 ccgcatttaa aggagatgac tctgttgtgc tttgtagtgattatcggcaa agccgcgatg 4740 cggccgccct aatcgctggc tgtgggttga aacttaaggtggattttagg cccattgggc 4800 tgtatgctgg tgttgttgtg gccccgggtc tcgggacccttcctgatgtt gttaggtttg 4860 ctgggcggct ctcggagaaa aactgggggc cgggttcagagagggcagaa cagctacggc 4920 tggctgtctg tgattttctg cgaaagttaa cgaatgtggctcaagtctgt gtggacgttg 4980 tttcgcaggt ttatggtgtt agccccggtt tggtacataacctgattggg atgctccaga 5040 ccattgctga tggcaaggcg cactttacag agacagttaaacctgtttta gacctcacca 5100 attctattat acatcgggtg gaatgaataa catgttcttttgctctgtgc atggagatgc 5160 caccatgcgc tctcgggctt ttctgttttt gttcctcgtgcttctgccta tgctgcccgc 5220 gccaccggcc ggtcagccgt ctggccgtcg ccgcgggcggcgcagcggcg gtgccggcgg 5280 tggtttctgg ggtgaccggg ttgattctca gcccttcgccctcccctata ttcatccaac 5340 caaccccttc gcatctgaca ttccagccgc agccggggctggagctcgcc ctcggcagcc 5400 agcccgtcca ctcggctccg cttggcgtga ccaatcccagcgccccgcca cttccgcccg 5460 tcgtcgatct gccccagctg gggcttcgcc gctgactgctgtggccccgg ccccagatac 5520 tgctcctgtt cccgatgtcg attctcgcgg cgctatattacgccgccagt ataatttatc 5580 aacatccccg ctaacatcta ctattgccac tggtactaaccttgttctat atgctgcccc 5640 gctgagccct ttgcttccgc tccaagatgg aactaacactcacattatgg ccactgaagc 5700 atcaaattat gcccagtacc gtgttgtccg cgccaccatccggtaccgtc cgcttgtgcc 5760 gaacgctgtc ggcggatacg ctatatctat ctctttctggcctcagacaa ctaccacccc 5820 gacatctgtg gatatgaatt ctatcacctc cacggatgtccgaatccttg tccagcctgg 5880 catcgcttca gaacttgtga tccctagtga gcgcctgcattatcgtaacc aaggctggcg 5940 ctcggttgag acctctggtg ttgcggagga ggaggcgacctccggccttg tcatgctttg 6000 catccatgga tcacctgtga attcttacac caatacgccttatactggtg cccttggctt 6060 gcttgatttc gcactcgagc tcgagttccg caatttgacacccggtaaca cgaacacacg 6120 tgtttcccgc tactcgagta gtgcgcgcca caagctacgccgagggcctg atggcactgc 6180 tgagttaact accactgctg ctacacgctt tatgaaggaccttcatttta cagggactaa 6240 tggagttggt gaagtcggtc gtggtatagc gctaactctgttcaatcttg ctgacacgct 6300 tctcggcggg ctcccgacag aattgatttc gtcggctggtggtcagttgt tttactctcg 6360 ccccgtcgtc tcagccaatg gcgagccgac agtgaagctttatacttcag tcgagaacgc 6420 tcagcaggat aagggtatag ctatcccaca tgatattgaccttggtgagt cccgtgttgt 6480 cattcaggat tacgataacc aacatgagca ggaccgtcccaccccttctc ctgctccctc 6540 tcggcccttt tctgtccttc gtgctaatga tgtgctatggctttcactta cagcagctga 6600 gtatgatcag actacctatg gctcctctac taaccccatgtatgtctctg atactgtgac 6660 atttgttaat gtggctactg gtgcccaggg ggtatctcgctctctggact ggtctaaagt 6720 tacccttgat gggcgcccac ttatgactat ccagcagtattctaagacct tctttgtcct 6780 gcctctccgt ggtaagctct ccttttggga ggctggtactactaaggccg gctaccctta 6840 taattataat actaccgcca gtgaccagat tttaattgagaatgcagctg gtcaccgtgt 6900 atgcatttca acctacacta ctaatcttgg atctggccctgtttctattt ctgccgtcgg 6960 tgtcctcgca cctcactctg cgctggccgc tttagaggacactgttgact atcctgcccg 7020 tgctcatact tttgatgatt tttgccctga gtgccgtgcactcggccttc agggttgtgc 7080 tttccaatcg actgttgctg agctacagcg ccttaaaatgaaggtgggta aaacccggga 7140 gtactgattt attctacttg taccttcctt ctgttctgttcttttatttt ycttttctgc 7200 gtyccgcgct ccctggaaaa aaaaaaaa 7228 48 7230DNA Hepatitis E Virus Japan JRA1(AP003430) 48 ggcagaccac gtatgtggtcgatgccatgg aggcccacca gttcattaag gctcctggca 60 ttactactgc catagagcaggctgctctgg ctgcggccaa ctccgccttg gcgaatgctg 120 tggtggttcg gccgtttttgtctcgcgtac aaaccgagat ccttattaat ttgatgcaac 180 cccggcagtt ggttttccgccctgaggtgc tttggaacca tcctattcag agggttatac 240 acaatgaatt agaacagtactgccgggccc gggccggtcg ttgcctggag attggggctc 300 atccaagatc tattaatgataaccccaatg ttttgcaccg gtgttttctc aggccggtcg 360 gtagggacgt ccagcgctggtattctgccc ccacccgcgg ccctgcagcc aactgccgcc 420 gctctgcatt gcgtggcctcccccctgtcg accgcactta ctgttttgat ggattttcca 480 gttgtgcttt cgccgcagagaccggcgtgg ccctttactc tctacatgac ctttggccag 540 ctgatgttgc ggaggctatggcccgccatg gaatgacacg tctttatgct gcactccacc 600 tccctcccga ggtgttgttaccacccggta cttaccacac aacctcgtat cttctgatcc 660 atgacggcaa ccgtgctgttgtgacttatg aaggtgatac tagtgcaggt tacaaccatg 720 acgtttccat acttcgtgcatggattcgca cgactaaaat agttggtgac catccgttgg 780 ttatagagcg tgtgcgggctattggttgtc attttgtgct gctgctcacc gcggcccctg 840 agccatcgcc catgccttacgtcccttacc cccgttccac ggaggtgtat gtccgatcta 900 tatttggccc tggtggctccccatccttgt ttccgtcagc ttgctctaca aaatctacct 960 tccatgctgt tccagttcacatatgggacc ggcttatgct ttttggtgcc accttggacg 1020 accaggcgtt ttgctgctcacggctcatga catacctccg tggcattagc tacaaagtca 1080 ctgtcggtgc gcttgttgctaatgaggggt ggaatgcctc tgaagatgcc ctcaccgcag 1140 taatcactgc agcctacttgaccatctgtc accagcgcta cctccgtacc caggcgatat 1200 ctaagggtat gcgccggttggaggttgagc acgcccagaa gtttattaca agactttaca 1260 gctggttatt tgagaagtctggtcgtgact acatccccgg ccgccaactt cagttctatg 1320 cccagtgccg gcggtggctatctgcgggct ttcacctaga ccccagagtg ctcgtctttg 1380 atgagtcagt gccctgccgctgtaggactt tcttaaagaa ggttgcgggt aaattctgtt 1440 gcttcatgcg gtggttagggcaggagtgta cttgtttctt agaaccagct gagggcttag 1500 ttggcgatca aggccatgataatgaggctt atgagggttc tgaggttgac caggccgagc 1560 ctgtacacct tgatgtgtcggggacctatg ctgtccacgg gcaccagctt gaggccctct 1620 acagggcact caacattccacacgatattg ctgctcgagc tgcccgatta acggctactg 1680 ttgagctcgc tgcaggccccgaccgtctgg agtgccgcac cgtgctcggg aacaagactt 1740 tccggacgac ggtgactgatggcgcccatc tagaagcgaa cggccctgag caatatgttc 1800 tgtcgttcga tgcctcccgccagtctatgg gggccgggtc ccatagcctc acttacgagc 1860 ttacacccgc cggcttgcaggttaagatct catctaatgg cctagactgc actgccgtat 1920 tcccccctgg tggcgcccctagcgcgccgc cgggggaggt ggcggctttt tgcagcgccc 1980 tctacaggta taacagattcacccagcggc attcgctgac cggcggtttg tggctacatc 2040 ccgaggggtt gctaggcgttttcccccctt tttcccctgg gcacatttgg gagtctgcca 2100 accccttctg cggtgagggtaccttgtata ctcgcacctg gtctacatct ggtttttcta 2160 gtgacttttc ccctcctgaggcggccgccc ctgcaccggc tgccgcccca gggtcgtcct 2220 cccccactcc accagtcagtgatatttggg tgttaccacc gctttcagag gagccccagg 2280 tgggtgcgcc gcctgcacctcccacccccg agcctgctcg gctgccctgc cccactaaac 2340 ctaacacccc cgtgcgtaagccaacggcac cgccgccttc tcgcacccgc cgccttcttt 2400 acacctatcc tgatggtgctaaggtgtatg cggggtcact gtttgagtca gattgtgatt 2460 ggctggtgaa tgcctctaacccgggccatc gtcctggggg tggcctctgt cacgcctttt 2520 accaacgttt tcccgaggcgttctatccaa ctgaatttat tatgcgtgag ggtcttgcag 2580 catacacctt gaccccgcgccctattatcc atgcagtggc ccccgactat agggttgagc 2640 agaatccaaa gaggcttgaggcagcgtacc gagaaacttg ctcccgccgc ggcaccgctg 2700 cctatccact tcttggctcaggtatatacc aggtccctgc tggtcttagt tttgatgcct 2760 gggagcgtaa ccatcgccctggcgatgagc tttacctgac tgaacccgct gcagcctggt 2820 ttgaagctaa taagccaacgcagccagcac ttacgataac ggaagataca gctcgcacgg 2880 ccaacctagc attagagatcgatgctgcca cagacgttgg ccgtgcttgt gccggctgca 2940 ctattagccc cgggattgtgcattatcagt tcactgccgg ggtcccaggc tcaggcaaat 3000 caaggtccat acagcagggggatgtcgatg ttgtggttgt ccccacccgg gaacttcgca 3060 atagctggcg ccgtcggggctttgcggcct ttacacccca cacggcggcc cgtgttacta 3120 taggccgccg tgttgttattgacgaggccc catcccttcc accgcacttg ttgctgttac 3180 acatgcagcg ggcctcctcagtccatctcc tcggtgaccc aaatcagatc cctgccatcg 3240 acttcgagca tgccggcctggtccccgcaa ttcgccctga gcttgcacca acgagctggt 3300 ggcatgttac gcatcgctgtccggccgatg tatgtgagct catacgcgga gcctacccta 3360 aaatccagac cacgagccgtgtgctacggt ctctgttctg gaatgagccg gctattggcc 3420 agaagttggt cttcacgcaggccgctaaag ctgccaaccc tggtgcaatt acggtccatg 3480 aagcccaggg tgctaccttcacagagacca caattatagc cacggctgat gccaggggtc 3540 ttattcagtc atcccgggcccatgctatag ttgcacttac ccgccacaca gagaagtgcg 3600 ttattttgga tgcccctggtttgttgcgcg aggtcggcat atcagatgta attgttaaca 3660 actttttcct tgctggcggagaggtgggcc atcaccgccc ctctgtgata cctcgtggca 3720 atcctgaccg gaaccttgacaccctacagg ccttcccgcc atcctgccaa attagtgctt 3780 accatcagtt ggctgaggagttaggccatc gcccggctcc tgttgctgcc gttttgcccc 3840 cctgccccga gctcgagcagggcttattgt atatgccaca ggagcttaca gtgtccgata 3900 gtgtgttggt ttttgagctcactgacatag tccattgccg catggctgcc ccaagtcagc 3960 ggaaggccgt cctctcaacacttgtgggga ggtatggccg caagacgaaa ttgtatgagg 4020 cagcccattc agatgttcgagagtctctag ctaggttcat tcccactatc ggacctgtcc 4080 aggccaccac gtgtgagttatatgaactgg ttgaggccat ggtggaaaag ggccaggacg 4140 gctctgccgt cctggagcttgatctatgta atcgtgatgt ttcgcgcatt acattctttc 4200 agaaagactg taataagtttacaactggtg agaccattgc ccatggtaag gttggccagg 4260 gcatatcggc ctggagtaagaccttttgcg ccctgtttgg tccgtggttt cgtgccattg 4320 aaaaagaaat actagccctgctcccgccta atatcttcta cggcgacgcc tacgaggagt 4380 cggtgtttgc cgcggccgtgtccggggcgg ggtcttgcat ggtatttgaa aatgactttt 4440 cggaatttga tagtactcagaacaatttct cccttggcct tgagtgtgtg gttatggaag 4500 agtgtggtat gccccaatggctgatcagat tgtatcacct ggtccggtca gcctggattc 4560 tgcaggcgcc aaaggagtctcttaaaggtt tctggaagaa gcattctggt gagcctggta 4620 cccttctctg gaacaccatctggaacatgg cgatcatagc ccattgctat gagtttcgcg 4680 atttccgggt cgccgcttttaagggtgatg actcggtagt cctctgtagt gattaccgac 4740 agagtcgtaa cgcggcagccttaatcgcag gttgtgggct caagttgaag gttgactatc 4800 gccctattgg gctgtacgctggtgtggtgg tggcccctgg cttggggaca ctgcctgatg 4860 tagtgcgatt tgctggccggctgtccgaaa agaattgggg ccctggccca gagcgtgctg 4920 agcagctgcg tcttgctgtctgtgacttcc ttcgagggtt aacgaatgtt gcgcaggttt 4980 gtgttgatgt tgtgtcccgtgtttatggag tcagccccgg gctggtacat aaccttattg 5040 gcatgctgca gaccattgctgatggcaagg cccactttac agagtcaatt aaacctgtgc 5100 ttgaccttac aaattctattatacagcggg tggaatgaat aacatgtctt gtgcatcgcc 5160 catgggatca ccatgcgccctagggctgtt ctgttgttgc tcttcgtgct tctgcctatg 5220 ctgcccgcgc caccggccggccagccgtct ggccgccgtc gtgggcggcg cagcggcggt 5280 gccggcggtg gtttctggggtgacagggtt gattctcagc ccttcgccct cccctatatt 5340 catccaacca accccttcgccgccgatgtc gtttcacaat ccggggctgg agctcgccct 5400 cgacagccgc cccgcccccttggctccgct tggcgcgacc agtcccagcg ccccaccgct 5460 gccccccgtc gtcgacctgccccagctggg gctgcgccgc tgactgctac atcaccagct 5520 cctgacacag ctcctgtgcctgatgtcgac tcacgcggcg ctattttgcg tcggcagtat 5580 aatctgtcca cgtccccgcttacgtcatct gtcgcctcgg gtactaattt ggttctctat 5640 gccgccccat tgaacccactcctacccctc caggatggca ccaacaccca catcatggct 5700 accgaggcat ctaattatgcccagtaccgg gtggttcgag ctacaatccg ttatcgcccg 5760 ttggtaccaa atgctgttggtggttatgcc atctctattt ccttttggcc tcagacaacc 5820 actaccccca cctctgttgatatgaattct attacctcta ctgatgttag gatcttagtc 5880 cagcccggta ttgcctccgagttggtcatt cccagtgagc gtcttcatta tcgtaatcaa 5940 ggctggcgct ctgtcgagaccacgggtgtc gccgaggagg aggctacctc tggcctggta 6000 atgctttgca ttcatgggtctcctgtcaat tcttacacaa atacacctta tactggagca 6060 ctggggcttc ttgattttgcattagagctt gagtttagga atttgacacc tgggaacact 6120 aatacccgtg tgtcccgatataccagcaca gcccgccacc ggctgcgccg tggtgccgac 6180 gggaccgctg agcttaccactacggcggcc acgcgtttta tgaaggacct gcatttcacc 6240 ggtacgaatg gagttggtgaggtgggccga ggcatagccc tgacactgtt caatcttgct 6300 gatacgcttc tcggtggtctgccgacagaa ttgatttcgt cggctggggg ccagttgttc 6360 tactcccgcc ctgtcgtctcagccaatggc gaaccgactg taaagttata tacatctgtt 6420 gagaatgcac agcaggataagggtatcacc atcccacacg atatagacct cggtgattct 6480 cgtgtggtca tccaggactatgataaccag cacgagcagg accgacctac cccctcaccc 6540 gccccctctc gtccattctcggttcttcgc gctaatgatg ttctgtggct ctctcttacc 6600 gctgccgagt atgaccagactacgtatggg tcatctacca accccatgta tgtctcggac 6660 acagtcacat ttgttaacgtggccactggt gctcaggctg ttgctcgctc ccttgattgg 6720 tctaaagtta ccttggacggtcgccccctc actactattc agcagtattc taagacattc 6780 tacgttctcc cgcttcgtggaaagttgtct ttttgggagg ctggcacgac caaggctggt 6840 tatccttata attataatacaactgctagt gatcagattt taatagagaa cgcagctggc 6900 catcgtgtcg ctatctctacttacactacc agcctgggcg ccggccccac ttctatctct 6960 gcggtcggtg tgttagccccgcactcagcc cttgctgttc ttgaggatac cgccgattac 7020 cccgctcgtg cccatacttttgatgacttc tgcccggaat gtcgcaccct tggtttgcag 7080 ggctgcgctt tccagtctactattgctgag cttcagcgcc ttaaaatgaa ggtaggtaaa 7140 acccgggagt tctaattaattcgtcctgta cccccttcgt agttttcttt tgctttattt 7200 ctcttttctg ctttccgcgctccctggaaa 7230 49 7180 DNA Hepatitis E Virus Mexico(M74506) 49gccatggagg cccaccagtt cattaaggct cctggcatca ctactgctat tgagcaagca 60gctctagcag cggccaactc cgcccttgcg aatgctgtgg tggtccggcc tttcctttcc 120catcagcagg ttgagatcct tataaatctc atgcaacctc ggcagctggt gtttcgtcct 180gaggtttttt ggaatcaccc gattcaacgt gttatacata atgagcttga gcagtattgc 240cgtgctcgct cgggtcgctg ccttgagatt ggagcccacc cacgctccat taatgataat 300cctaatgtcc tccatcgctg ctttctccac cccgtcggcc gggatgttca gcgctggtac 360acagccccga ctaggggacc tgcggcgaac tgtcgccgct cggcacttcg tggtctgcca 420ccagccgacc gcacttactg ttttgatggc tttgccggct gccgttttgc cgccgagact 480ggtgtggctc tctattctct ccatgacttg cagccggctg atgttgccga ggcgatggct 540cgccacggca tgacccgcct ttatgcagct ttccacttgc ctccagaggt gctcctgcct 600cctggcacct accggacatc atcctacttg ctgatccacg atggtaagcg cgcggttgtc 660acttatgagg gtgacactag cgccggttac aatcatgatg ttgccaccct ccgcacatgg 720atcaggacaa ctaaggttgt gggtgaacac cctttggtga tcgagcgggt gcggggtatt 780ggctgtcact ttgtgttgtt gatcactgcg gcccctgagc cctccccgat gccctacgtt 840ccttacccgc gttcgacgga ggtctatgtc cggtctatct ttgggcccgg cgggtccccg 900tcgctgttcc cgaccgcttg tgctgtcaag tccacttttc acgccgtccc cacgcacatc 960tgggaccgtc tcatgctctt tggggccacc ctcgacgacc aggccttttg ctgctccagg 1020cttatgacgt accttcgtgg cattagctat aaggtaactg tgggtgccct ggtcgctaat 1080gaaggctgga atgccaccga ggatgcgctc actgcagtta ttacggcggc ttacctcaca 1140atatgtcatc agcgttattt gcggacccag gcgatttcta agggcatgcg ccggcttgag 1200cttgaacatg ctcagaaatt tatttcacgc ctctacagct ggctatttga gaagtcaggt 1260cgtgattaca tcccaggccg ccagctgcag ttctacgctc agtgccgccg ctggttatct 1320gccgggttcc atctcgaccc ccgcacctta gtttttgatg agtcagtgcc ttgtagctgc 1380cgaaccacca tccggcggat cgctggaaaa ttttgctgtt ttatgaagtg gctcggtcag 1440gagtgttctt gtttcctcca gcccgccgag gggctggcgg gcgaccaagg tcatgacaat 1500gaggcctatg aaggctctga tgttgatact gctgagcctg ccaccctaga cattacaggc 1560tcatacatcg tggatggtcg gtctctgcaa actgtctatc aagctctcga cctgccagct 1620gacctggtag ctcgcgcagc ccgactgtct gctacagtta ctgttactga aacctctggc 1680cgtctggatt gccaaacaat gatcggcaat aagacttttc tcactacctt tgttgatggg 1740gcacgccttg aggttaacgg gcctgagcag cttaacctct cttttgacag ccagcagtgt 1800agtatggcag ccggcccgtt ttgcctcacc tatgctgccg tagatggcgg gctggaagtt 1860catttttcca ccgctggcct cgagagccgt gttgttttcc cccctggtaa tgccccgact 1920gccccgccga gtgaggtcac cgccttctgc tcagctcttt ataggcacaa ccggcagagc 1980cagcgccagt cggttattgg tagtttgtgg ctgcaccctg aaggtttgct cggcctgttc 2040ccgccctttt cacccgggca tgagtggcgg tctgctaacc cattttgcgg cgagagcacg 2100ctctacaccc gcacttggtc cacaattaca gacacaccct taactgtcgg gctaatttcc 2160ggtcatttgg atgctgctcc ccactcgggg gggccacctg ctactgccac aggccctgct 2220gtaggctcgt ctgactctcc agaccctgac ccgctacctg atgttacaga tggctcacgc 2280ccctctgggg cccgtccggc tggccccaac ccgaatggcg ttccgcagcg ccgcttacta 2340cacacctacc ctgacggcgc taagatctat gtcggctcca ttttcgagtc tgagtgcacc 2400tggcttgtca acgcatctaa cgccggccac cgccctggtg gcgggctttg tcatgctttt 2460tttcagcgtt accctgattc gtttgacgcc accaagtttg tgatgcgtga tggtcttgcc 2520gcgtataccc ttacaccccg gccgatcatt catgcggtgg ccccggacta tcgattggaa 2580cataacccca agaggctcga ggctgcctac cgcgagactt gcgcccgccg aggcactgct 2640gcctatccac tcttaggcgc tggcatttac caggtgcctg ttagtttgag ttttgatgcc 2700tgggagcgga accaccgccc gtttgacgag ctttacctaa cagagctggc ggctcggtgg 2760tttgaatcca accgccccgg tcagcccacg ttgaacataa ctgaggatac cgcccgtgcg 2820gccaacctgg ccctggagct tgactccggg agtgaagtag gccgcgcatg tgccgggtgt 2880aaagtcgagc ctggcgttgt gcggtatcag tttacagccg gtgtccccgg ctctggcaag 2940tcaaagtccg tgcaacaggc ggatgtggat gttgttgttg tgcccactcg cgagcttcgg 3000aacgcttggc ggcgccgggg ctttgcggca ttcactccgc acactgcggc ccgtgtcact 3060agcggccgta gggttgtcat tgatgaggcc ccttcgctcc ccccacactt gctgctttta 3120catatgcagc gtgctgcatc tgtgcacctc cttggggacc cgaatcagat ccccgccata 3180gattttgagc acaccggtct gattccagca atacggccgg agttggtccc gacttcatgg 3240tggcatgtca cccaccgttg ccctgcagat gtctgtgagt tagtccgtgg tgcttaccct 3300aaaatccaga ctacaagtaa ggtgctccgt tcccttttct ggggagagcc agctgtcggc 3360cagaagctag tgttcacaca ggctgctaag gccgcgcacc ccggatctat aacggtccat 3420gaggcccagg gtgccacttt taccactaca actataattg caactgcaga tgcccgtggc 3480ctcatacagt cctcccgggc tcacgctata gttgctctca ctaggcatac tgaaaaatgt 3540gttatacttg actctcccgg cctgttgcgt gaggtgggta tctcagatgc cattgttaat 3600aatttcttcc tttcgggtgg cgaggttggt caccagagac catcggtcat tccgcgaggc 3660aaccctgacc gcaatgttga cgtgcttgcg gcgtttccac cttcatgcca aataagcgcc 3720ttccatcagc ttgctgagga gctgggccac cggccggcgc cggtggcggc tgtgctacct 3780ccctgccctg agcttgagca gggccttctc tatctgccac aggagctagc ctcctgtgac 3840agtgttgtga catttgagct aactgacatt gtgcactgcc gcatggcggc ccctagccaa 3900aggaaagctg ttttgtccac gctggtaggc cggtatggca gacgcacaag gctttatgat 3960gcgggtcaca ccgatgtccg cgcctccctt gcgcgcttta ttcccactct cgggcgggtt 4020actgccacca cctgtgaact ctttgagctt gtagaggcga tggtggagaa gggccaagac 4080ggttcagccg tcctcgagtt ggatttgtgc agccgagatg tctcccgcat aacctttttc 4140cagaaggatt gtaacaagtt cacgaccggc gagacaattg cgcatggcaa agtcggtcag 4200ggtatcttcc gctggagtaa gacgttttgt gccctgtttg gcccctggtt ccgtgcgatt 4260gagaaggcta ttctatccct tttaccacaa gctgtgttct acggggatgc ttatgacgac 4320tcagtattct ctgctgccgt ggctggcgcc agccatgcca tggtgtttga aaatgatttt 4380tctgagtttg actcgactca gaataacttt tccctaggtc ttgagtgcgc cattatggaa 4440gagtgtggta tgccccagtg gcttgtcagg ttgtaccatg ccgtccggtc ggcgtggatc 4500ctgcaggccc caaaagagtc tttgagaggg ttctggaaga agcattctgg tgagccgggc 4560agcttgctct ggaatacggt gtggaacatg gcaatcattg cccattgcta tgagttccgg 4620gacctccagg ttgccgcctt caagggcgac gactcggtcg tcctctgtag tgaataccgc 4680cagagcccag gcgccggttc gcttatagca ggctgtggtt tgaagttgaa ggctgacttc 4740cggccgattg ggctgtatgc cggggttgtc gtcgccccgg ggctcggggc cctacccgat 4800gtcgttcgat tcgccggacg gctttcggag aagaactggg ggcctgatcc ggagcgggca 4860gagcagctcc gcctcgccgt gcaggatttc ctccgtaggt taacgaatgt ggcccagatt 4920tgtgttgagg tggtgtctag agtttacggg gtttccccgg gtctggttca taacctgata 4980ggcatgctcc agactattgg tgatggtaag gcgcatttta cagagtctgt taagcctata 5040cttgacctta cacactcaat tatgcaccgg tctgaatgaa taacatgtgg tttgctgcgc 5100ccatgggttc gccaccatgc gccctaggcc tcttttgctg ttgttcctct tgtttctgcc 5160tatgttgccc gcgccaccga ccggtcagcc gtctggccgc cgtcgtgggc ggcgcagcgg 5220cggtaccggc ggtggtttct ggggtgaccg ggttgattct cagcccttcg caatccccta 5280tattcatcca accaacccct ttgccccaga cgttgccgct gcgtccgggt ctggacctcg 5340ccttcgccaa ccagcccggc cacttggctc cacttggcga gatcaggccc agcgcccctc 5400cgctgcctcc cgtcgccgac ctgccacagc cggggctgcg gcgctgacgg ctgtggcgcc 5460tgcccatgac acctcacccg tcccggacgt tgattctcgc ggtgcaattc tacgccgcca 5520gtataatttg tctacttcac ccctgacatc ctctgtggcc tctggcacta atttagtcct 5580gtatgcagcc ccccttaatc cgcctctgcc gctgcaggac ggtactaata ctcacattat 5640ggccacagag gcctccaatt atgcacagta ccgggttgcc cgcgctacta tccgttaccg 5700gcccctagtg cctaatgcag ttggaggcta tgctatatcc atttctttct ggcctcaaac 5760aaccacaacc cctacatctg ttgacatgaa ttccattact tccactgatg tcaggattct 5820tgttcaacct ggcatagcat ctgaattggt catcccaagc gagcgccttc actaccgcaa 5880tcaaggttgg cgctcggttg agacatctgg tgttgctgag gaggaagcca cctccggtct 5940tgtcatgtta tgcatacatg gctctccagt taactcctat accaataccc cttataccgg 6000tgcccttggc ttactggact ttgccttaga gcttgagttt cgcaatctca ccacctgtaa 6060caccaataca cgtgtgtccc gttactccag cactgctcgt cactccgccc gaggggccga 6120cgggactgcg gagctgacca caactgcagc caccaggttc atgaaagatc tccactttac 6180cggccttaat ggggtaggtg aagtcggccg cgggatagct ctaacattac ttaaccttgc 6240tgacacgctc ctcggcgggc tcccgacaga attaatttcg tcggctggcg ggcaactgtt 6300ttattcccgc ccggttgtct cagccaatgg cgagccaacc gtgaagctct atacatcagt 6360ggagaatgct cagcaggata agggtgttgc tatcccccac gatatcgatc ttggtgattc 6420gcgtgtggtc attcaggatt atgacaacca gcatgagcag gatcggccca ccccgtcgcc 6480tgcgccatct cggccttttt ctgttctccg agcaaatgat gtactttggc tgtccctcac 6540tgcagccgag tatgaccagt ccacttacgg gtcgtcaact ggcccggttt atatctcgga 6600cagcgtgact ttggtgaatg ttgcgactgg cgcgcaggcc gtagcccgat cgcttgactg 6660gtccaaagtc accctcgacg ggcggcccct cccgactgtt gagcaatatt ccaagacatt 6720ctttgtgctc ccccttcgtg gcaagctctc cttttgggag gccggcacaa caaaagcagg 6780ttatccttat aattataata ctactgctag tgaccagatt ctgattgaaa atgctgccgg 6840ccatcgggtc gccatttcaa cctataccac caggcttggg gccggtccgg tcgccatttc 6900tgcggccgcg gttttggctc cacgctccgc cctggctctg ctggaggata cttttgatta 6960tccggggcgg gcgcacacat ttgatgactt ctgccctgaa tgccgcgctt taggcctcca 7020gggttgtgct ttccagtcaa ctgtcgctga gctccagcgc cttaaagtta aggtgggtaa 7080aactcgggag ttgtagttta tttggctgtg cccacctact tatatctgct gatttccttt 7140atttcctttt tctcggtccc gcgctccctg aaaaaaaaaa 7180 50 1709 PRT Hepatitis EVirus JKN-Sap (ORF1) 50 Met Glu Ala His Gln Phe Ile Lys Ala Pro Gly IleThr Thr Ala Ile 1 5 10 15 Glu Gln Ala Ala Leu Ala Ala Ala Asn Ser AlaLeu Ala Asn Ala Val 20 25 30 Val Val Arg Pro Phe Leu Ser Arg Val Gln ThrGlu Ile Leu Ile Asn 35 40 45 Leu Met Gln Pro Arg Gln Leu Val Phe Arg ProGlu Val Leu Trp Asn 50 55 60 His Pro Ile Gln Arg Val Ile His Asn Glu LeuGlu Gln Tyr Cys Arg 65 70 75 80 Ala Arg Ala Gly Arg Cys Leu Glu Val GlyAla His Pro Arg Ser Ile 85 90 95 Asn Asp Asn Pro Asn Val Leu His Arg CysPhe Leu Arg Pro Val Gly 100 105 110 Arg Asp Val Gln Arg Trp Tyr Ser AlaPro Thr Arg Gly Pro Ala Ala 115 120 125 Asn Cys Arg Arg Ser Ala Leu ArgGly Leu Pro Pro Ala Asp Arg Thr 130 135 140 Tyr Cys Phe Asp Gly Phe SerArg Cys Ala Phe Ala Ala Glu Thr Gly 145 150 155 160 Val Ala Leu Tyr SerLeu His Asp Leu Trp Pro Ala Asp Val Ala Glu 165 170 175 Ala Met Ala ArgHis Gly Met Thr Arg Leu Tyr Ala Ala Leu His Leu 180 185 190 Pro Pro GluVal Leu Leu Pro Pro Gly Thr Tyr His Thr Thr Ser Tyr 195 200 205 Leu LeuIle His Asp Gly Asp Arg Ala Val Val Thr Tyr Glu Gly Asp 210 215 220 ThrSer Ala Gly Tyr Asn His Asp Val Ser Ile Leu Arg Ala Trp Ile 225 230 235240 Arg Thr Thr Lys Ile Val Gly Asp His Pro Leu Val Ile Glu Arg Val 245250 255 Arg Ala Ile Gly Cys His Phe Val Leu Leu Leu Thr Ala Ala Pro Glu260 265 270 Pro Ser Pro Met Pro Tyr Val Pro Tyr Pro Arg Ser Thr Glu ValTyr 275 280 285 Val Arg Ser Ile Phe Gly Pro Gly Gly Ser Pro Ser Leu PhePro Ser 290 295 300 Ala Cys Ser Thr Lys Ser Thr Phe His Ala Val Pro ValHis Ile Trp 305 310 315 320 Asp Arg Leu Met Leu Phe Gly Ala Thr Leu AspAsp Gln Ala Phe Cys 325 330 335 Cys Ser Arg Leu Met Thr Tyr Leu Arg GlyIle Ser Tyr Lys Val Thr 340 345 350 Val Gly Ala Leu Val Ala Asn Glu GlyTrp Asn Ala Ser Glu Asp Ala 355 360 365 Leu Thr Ala Val Ile Thr Ala AlaTyr Leu Thr Ile Cys His Gln Arg 370 375 380 Tyr Leu Arg Thr Gln Ala IleSer Lys Gly Met Arg Arg Leu Glu Val 385 390 395 400 Glu His Ala Gln LysPhe Ile Thr Arg Leu Tyr Ser Trp Leu Phe Glu 405 410 415 Lys Ser Gly ArgAsp Tyr Ile Pro Gly Arg Gln Leu Gln Phe Tyr Ala 420 425 430 Gln Cys ArgArg Trp Leu Ser Ala Gly Phe His Leu Asp Pro Arg Val 435 440 445 Leu ValPhe Asp Glu Ala Val Pro Cys Arg Cys Arg Thr Phe Leu Lys 450 455 460 LysVal Ala Gly Lys Phe Cys Cys Phe Met Arg Trp Leu Gly Gln Glu 465 470 475480 Cys Thr Cys Phe Leu Glu Pro Ala Glu Gly Leu Ile Gly Asp Gln Gly 485490 495 His Asp Asn Glu Ala Tyr Glu Gly Ser Glu Val Asp Pro Ala Glu Pro500 505 510 Ala His Leu Asp Val Ser Gly Thr Tyr Ala Val His Gly His GlnLeu 515 520 525 Glu Ala Leu Tyr Arg Ala Leu Asn Val Pro His Asp Ile AlaAla Arg 530 535 540 Ala Ser Arg Leu Thr Ala Thr Val Glu Leu Val Ala SerPro Asp Arg 545 550 555 560 Leu Glu Cys Arg Thr Val Leu Gly Asn Lys ThrPhe Arg Thr Thr Val 565 570 575 Val Asp Gly Ala His Leu Glu Ala Asn GlyPro Glu Glu Tyr Val Leu 580 585 590 Ser Phe Asp Ala Ser Arg Gln Ser MetGly Ala Gly Ser His Ser Leu 595 600 605 Thr Tyr Glu Leu Thr Pro Ala GlyLeu Gln Val Arg Ile Ser Ser Asn 610 615 620 Gly Leu Asp Cys Thr Ala ValPhe Pro Pro Gly Gly Ala Pro Ser Ala 625 630 635 640 Ala Pro Gly Glu ValAla Ala Phe Cys Ser Ala Leu Tyr Arg Tyr Asn 645 650 655 Arg Phe Thr GlnArg His Ser Leu Thr Gly Gly Leu Trp Leu His Pro 660 665 670 Glu Gly LeuLeu Gly Ile Phe Pro Pro Phe Ser Pro Gly His Ile Trp 675 680 685 Glu SerAla Asn Pro Phe Cys Gly Glu Gly Thr Leu Tyr Thr Arg Thr 690 695 700 TrpSer Thr Ser Gly Phe Ser Ser Asp Phe Ser Pro Pro Glu Ala Ala 705 710 715720 Ala Pro Val Pro Ala Ala Ala Pro Gly Leu Pro His Pro Thr Pro Pro 725730 735 Val Ser Asp Ile Trp Val Leu Pro Pro Pro Ser Glu Glu Ser Gln Ile740 745 750 Asp Ala Ala Pro Val Pro Pro Val Pro Lys Thr Val Gly Leu ProSer 755 760 765 Pro Ile Val Leu Ala Pro Pro Ser Pro Leu Pro Ser Pro ValArg Lys 770 775 780 Pro Pro Ser Pro Pro Pro Ser Arg Thr Arg Arg Leu LeuTyr Thr Tyr 785 790 795 800 Pro Asp Gly Ala Arg Val Tyr Ala Gly Ser LeuPhe Glu Ser Asp Cys 805 810 815 Asp Trp Leu Val Asn Ala Ser Asn Pro GlyHis Arg Pro Gly Gly Gly 820 825 830 Leu Cys His Ala Phe Tyr Gln Arg PhePro Glu Ala Phe Tyr Pro Thr 835 840 845 Glu Phe Ile Met Arg Glu Gly LeuAla Ala Tyr Thr Leu Thr Pro Arg 850 855 860 Pro Ile Ile His Ala Val AlaPro Asp Tyr Arg Val Glu Gln Asn Pro 865 870 875 880 Lys Arg Leu Glu AlaAla Tyr Arg Glu Thr Cys Ser Arg Arg Gly Thr 885 890 895 Ala Ala Tyr ProLeu Leu Gly Ser Gly Ile Tyr Gln Val Pro Val Ser 900 905 910 Leu Ser PheAsp Ala Trp Glu Arg Asn His Arg Pro Gly Asp Glu Leu 915 920 925 Tyr LeuThr Glu Pro Ala Ala Ala Trp Phe Glu Ala Asn Lys Pro Ser 930 935 940 GlnPro Ala Leu Thr Ile Thr Glu Asp Thr Ala Arg Thr Ala Asn Leu 945 950 955960 Ala Leu Glu Ile Asp Ala Ala Thr Glu Val Gly Arg Ala Cys Ala Gly 965970 975 Cys Thr Ile Ser Pro Gly Val Val His Tyr Gln Phe Thr Ala Gly Val980 985 990 Pro Gly Ser Gly Lys Ser Arg Ser Ile Gln Gln Gly Asp Val AspVal 995 1000 1005 Val Val Val Pro Thr Arg Glu Leu Arg Asn Ser Trp ArgArg Arg Gly 1010 1015 1020 Phe Ala Ala Phe Thr Pro His Thr Ala Ala ArgVal Thr Ile Gly Arg 1025 1030 1035 1040 Arg Val Val Ile Asp Glu Ala ProSer Leu Pro Pro His Leu Leu Leu 1045 1050 1055 Leu His Met Gln Arg AlaSer Ser Val His Leu Leu Gly Asp Pro Asn 1060 1065 1070 Gln Ile Pro AlaIle Asp Phe Glu His Ala Gly Leu Val Pro Ala Ile 1075 1080 1085 Arg ProGlu Leu Ala Pro Thr Ser Trp Trp His Val Thr His Arg Cys 1090 1095 1100Pro Ala Asp Val Cys Glu Leu Ile Arg Gly Ala Tyr Pro Lys Ile Gln 11051110 1115 1120 Thr Thr Ser Arg Val Leu Arg Ser Leu Phe Trp Asn Glu ProAla Ile 1125 1130 1135 Gly Gln Lys Leu Val Phe Thr Gln Ala Ala Lys AlaAla Asn Pro Gly 1140 1145 1150 Ala Ile Thr Val His Glu Ala Gln Gly AlaThr Phe Thr Glu Thr Thr 1155 1160 1165 Ile Ile Ala Thr Ala Asp Ala ArgGly Leu Ile Gln Ser Ser Arg Ala 1170 1175 1180 His Ala Ile Val Ala LeuThr Arg His Thr Glu Lys Cys Val Ile Leu 1185 1190 1195 1200 Asp Ala ProGly Leu Leu Arg Glu Val Gly Ile Ser Asp Val Ile Val 1205 1210 1215 AsnAsn Phe Phe Leu Ala Gly Gly Glu Val Gly His His Arg Pro Ser 1220 12251230 Val Ile Pro Arg Gly Asn Pro Asp Gln Asn Leu Gly Thr Leu Gln Ala1235 1240 1245 Phe Pro Pro Ser Cys Gln Ile Ser Ala Tyr His Gln Leu AlaGlu Glu 1250 1255 1260 Leu Gly His Arg Pro Ala Pro Val Ala Ala Val LeuPro Pro Cys Pro 1265 1270 1275 1280 Glu Leu Glu Gln Gly Leu Leu Tyr MetPro Gln Glu Leu Thr Val Ser 1285 1290 1295 Asp Ser Val Leu Val Phe GluLeu Thr Asp Ile Val His Cys Arg Met 1300 1305 1310 Ala Ala Pro Ser GlnArg Lys Ala Val Leu Ser Thr Leu Val Gly Arg 1315 1320 1325 Tyr Gly ArgArg Thr Lys Leu Tyr Glu Ala Ala His Ser Asp Val Arg 1330 1335 1340 GluSer Leu Ala Arg Phe Ile Pro Thr Ile Gly Pro Val Gln Ala Thr 1345 13501355 1360 Thr Cys Glu Leu Tyr Glu Leu Val Glu Ala Met Val Glu Lys GlyGln 1365 1370 1375 Asp Gly Ser Ala Val Leu Glu Leu Asp Leu Cys Asn ArgAsp Val Ser 1380 1385 1390 Arg Ile Thr Phe Phe Gln Lys Asp Cys Asn LysPhe Thr Thr Gly Glu 1395 1400 1405 Thr Ile Ala His Gly Lys Val Gly GlnGly Ile Ser Ala Trp Ser Lys 1410 1415 1420 Thr Phe Cys Ala Leu Phe GlyPro Trp Phe Arg Ala Ile Glu Lys Glu 1425 1430 1435 1440 Ile Leu Ala LeuLeu Pro Pro Asn Ile Phe Tyr Gly Asp Ala Tyr Glu 1445 1450 1455 Glu SerVal Phe Ala Ala Ala Val Ser Gly Ala Gly Ser Cys Met Val 1460 1465 1470Phe Glu Asn Asp Phe Ser Glu Phe Asp Ser Thr Gln Asn Asn Phe Ser 14751480 1485 Leu Gly Leu Glu Cys Val Val Met Glu Glu Cys Gly Met Pro GlnTrp 1490 1495 1500 Leu Ile Arg Leu Tyr His Leu Val Arg Ser Ala Trp IleLeu Gln Ala 1505 1510 1515 1520 Pro Lys Glu Ser Leu Lys Gly Phe Trp LysLys His Ser Gly Glu Pro 1525 1530 1535 Gly Thr Leu Leu Trp Asn Thr ValTrp Asn Met Ala Ile Ile Ala His 1540 1545 1550 Cys Tyr Glu Phe Arg AspPhe Arg Val Ala Ala Phe Lys Gly Asp Asp 1555 1560 1565 Ser Val Val LeuCys Ser Asp Tyr Arg Gln Ser Arg Asn Ala Ala Ala 1570 1575 1580 Leu IleAla Gly Cys Gly Leu Lys Leu Lys Val Asp Tyr Arg Pro Ile 1585 1590 15951600 Gly Leu Tyr Ala Gly Val Val Val Ala Pro Gly Leu Gly Thr Leu Pro1605 1610 1615 Asp Val Val Arg Phe Ala Gly Arg Leu Ser Glu Lys Asn TrpGly Pro 1620 1625 1630 Gly Pro Glu Arg Ala Glu Gln Leu Arg Leu Ala ValCys Asp Phe Leu 1635 1640 1645 Arg Gly Leu Thr Asn Val Ala Gln Val CysVal Asp Val Val Ser Arg 1650 1655 1660 Val Tyr Gly Val Ser Pro Gly LeuVal His Asn Leu Ile Gly Met Leu 1665 1670 1675 1680 Gln Thr Ile Ala AspGly Lys Ala His Phe Thr Glu Thr Ile Lys Pro 1685 1690 1695 Val Leu AspLeu Thr Asn Ser Ile Ile Gln Arg Glu Glu 1700 1705 51 660 PRT Hepatitis EVirus JKN-Sap (ORF2) 51 Met Arg Pro Arg Ala Val Leu Leu Leu Phe Leu ValLeu Leu Pro Met 1 5 10 15 Leu Pro Ala Pro Pro Ala Gly Gln Pro Ser GlyArg Arg Arg Gly Arg 20 25 30 Arg Ser Gly Gly Ala Gly Gly Gly Phe Trp GlyAsp Arg Val Asp Ser 35 40 45 Gln Pro Phe Ala Leu Pro Tyr Ile His Pro ThrAsn Pro Phe Ala Ala 50 55 60 Asp Val Val Ser Gln Pro Gly Ala Gly Thr ArgPro Arg Gln Pro Pro 65 70 75 80 Arg Pro Leu Gly Ser Ala Trp Arg Asp GlnSer Gln Arg Pro Ser Ala 85 90 95 Ala Pro Arg Arg Arg Ser Ala Pro Ala GlyAla Ala Pro Leu Thr Ala 100 105 110 Val Ser Pro Ala Pro Asp Thr Ala ProVal Pro Asp Val Asp Ser Arg 115 120 125 Gly Ala Ile Leu Arg Arg Gln TyrAsn Leu Ser Thr Ser Pro Leu Thr 130 135 140 Ser Ser Val Ala Ser Gly ThrAsn Leu Val Leu Tyr Ala Ala Pro Leu 145 150 155 160 Asn Pro Leu Leu ProLeu Gln Asp Gly Thr Asn Thr His Ile Met Ala 165 170 175 Thr Glu Ala SerAsn Tyr Ala Gln Tyr Arg Val Val Arg Ala Thr Ile 180 185 190 Arg Tyr ArgPro Leu Val Pro Asn Ala Val Gly Gly Tyr Ala Ile Ser 195 200 205 Ile SerPhe Trp Pro Gln Thr Thr Thr Thr Pro Thr Ser Val Asp Met 210 215 220 AsnSer Ile Thr Ser Thr Asp Val Arg Ile Leu Val Gln Pro Gly Ile 225 230 235240 Ala Ser Glu Leu Val Ile Pro Ser Glu Arg Leu His Tyr Arg Asn Gln 245250 255 Gly Trp Arg Ser Val Glu Thr Thr Gly Val Ala Glu Glu Glu Ala Thr260 265 270 Ser Gly Leu Val Met Leu Cys Ile His Gly Ser Pro Val Asn SerTyr 275 280 285 Thr Asn Thr Pro Tyr Thr Gly Ala Leu Gly Leu Leu Asp PheAla Leu 290 295 300 Glu Leu Glu Phe Arg Asn Leu Thr Pro Gly Asn Thr AsnThr Arg Val 305 310 315 320 Ser Arg Tyr Thr Ser Thr Ala Arg His Arg LeuArg Arg Gly Ala Asp 325 330 335 Gly Thr Ala Glu Leu Thr Thr Thr Ala AlaThr Arg Phe Met Lys Asp 340 345 350 Leu His Phe Thr Gly Thr Asn Gly ValGly Glu Val Gly Arg Gly Ile 355 360 365 Ala Leu Thr Leu Phe Asn Leu AlaAsp Thr Leu Leu Gly Gly Leu Pro 370 375 380 Thr Glu Leu Ile Ser Ser AlaGly Gly Gln Leu Phe Tyr Ser Arg Pro 385 390 395 400 Val Val Ser Ala AsnGly Glu Pro Thr Val Lys Leu Tyr Thr Ser Val 405 410 415 Glu Asn Ala GlnGln Asp Lys Gly Ile Thr Ile Pro His Asp Ile Asp 420 425 430 Leu Gly AspSer Arg Val Val Ile Gln Asp Tyr Asp Asn Gln His Glu 435 440 445 Gln AspArg Pro Thr Pro Ser Pro Ala Pro Ser Arg Pro Phe Ser Val 450 455 460 LeuArg Ala Asn Asp Val Leu Trp Leu Ser Leu Thr Ala Ala Glu Tyr 465 470 475480 Asp Gln Thr Thr Tyr Gly Ser Ser Thr Asn Pro Met Tyr Val Ser Asp 485490 495 Thr Val Thr Leu Val Asn Val Ala Thr Gly Ala Gln Ala Val Ala Arg500 505 510 Ser Leu Asp Trp Ser Lys Val Thr Leu Asp Gly Arg Pro Leu ThrThr 515 520 525 Ile Gln Gln Tyr Ser Lys Thr Phe Tyr Val Leu Pro Leu ArgGly Lys 530 535 540 Leu Ser Phe Trp Glu Ala Gly Thr Thr Lys Ala Gly TyrPro Tyr Asn 545 550 555 560 Tyr Asn Thr Thr Ala Ser Asp Gln Ile Leu IleGlu Asn Ala Ala Gly 565 570 575 His Arg Val Ala Ile Ser Thr Tyr Thr ThrSer Leu Gly Ala Gly Pro 580 585 590 Thr Ser Ile Ser Ala Val Gly Val LeuAla Pro His Ser Ala Leu Ala 595 600 605 Val Leu Glu Asp Thr Val Asp TyrPro Ala Arg Ala His Thr Phe Asp 610 615 620 Asp Phe Cys Pro Glu Cys ArgThr Leu Gly Leu Gln Gly Cys Ala Phe 625 630 635 640 Gln Ser Thr Ile AlaGlu Leu Gln Arg Leu Lys Met Lys Val Gly Lys 645 650 655 Thr Arg Glu Ser660 52 1709 PRT Hepatitis E Virus JMY-Haw (ORF1) 52 Met Glu Ala His GlnPhe Ile Lys Ala Pro Gly Ile Thr Thr Ala Ile 1 5 10 15 Glu Gln Ala AlaLeu Ala Ala Ala Asn Ser Ala Leu Ala Asn Ala Val 20 25 30 Val Val Arg ProPhe Leu Ser Arg Val Gln Thr Glu Ile Leu Ile Asn 35 40 45 Leu Met Gln ProArg Gln Leu Val Phe Arg Pro Glu Val Leu Trp Asn 50 55 60 His Pro Ile GlnArg Val Ile His Asn Glu Leu Glu Gln Tyr Cys Arg 65 70 75 80 Ala Arg AlaGly Arg Cys Leu Glu Val Gly Ala His Pro Arg Ser Ile 85 90 95 Asn Asp AsnPro Asn Val Leu His Arg Cys Phe Leu Arg Pro Val Gly 100 105 110 Arg AspVal Gln Arg Trp Tyr Ser Ala Pro Thr Arg Gly Pro Ala Ala 115 120 125 AsnCys Arg Arg Ser Ala Leu Arg Gly Leu Pro Pro Ala Asp Arg Thr 130 135 140Tyr Cys Phe Asp Gly Phe Ser Arg Cys Ala Phe Ala Ala Glu Thr Gly 145 150155 160 Val Ala Leu Tyr Ser Leu His Asp Leu Trp Pro Ala Asp Val Ala Glu165 170 175 Ala Met Ala Arg His Gly Met Thr Arg Leu Tyr Ala Val Leu HisLeu 180 185 190 Pro Pro Glu Val Leu Leu Pro Pro Gly Thr Tyr His Thr ThrSer Tyr 195 200 205 Leu Leu Ile His Asp Gly Asp Arg Ala Val Val Thr TyrGlu Gly Asp 210 215 220 Thr Ser Ala Gly Tyr Asn His Asp Val Ser Ile LeuArg Ala Trp Ile 225 230 235 240 Arg Thr Thr Lys Ile Val Gly Asp His ProLeu Val Ile Glu Arg Val 245 250 255 Arg Ala Ile Gly Cys His Phe Val LeuLeu Leu Thr Ala Ala Pro Glu 260 265 270 Pro Ser Pro Met Pro Tyr Val ProTyr Pro Arg Ser Thr Glu Val Tyr 275 280 285 Val Arg Ser Ile Phe Gly ProGly Gly Ser Pro Ser Leu Phe Pro Ser 290 295 300 Ala Cys Ser Thr Lys SerThr Phe His Ala Val Pro Val His Ile Trp 305 310 315 320 Asp Arg Leu MetLeu Phe Gly Ala Thr Leu Asp Asp Gln Ala Phe Cys 325 330 335 Cys Ser ArgLeu Met Thr Tyr Leu Arg Gly Ile Ser Tyr Lys Val Thr 340 345 350 Val GlyAla Leu Val Ala Asn Glu Gly Trp Asn Ala Ser Glu Asp Ala 355 360 365 LeuThr Ala Val Ile Thr Ala Ala Tyr Leu Thr Ile Cys His Gln Arg 370 375 380Tyr Leu Arg Thr Gln Ala Ile Ser Lys Gly Met Arg Arg Leu Glu Val 385 390395 400 Glu His Ala Gln Lys Phe Ile Thr Arg Leu Tyr Ser Trp Leu Phe Glu405 410 415 Lys Ser Gly Arg Asp Tyr Ile Pro Gly Arg Gln Leu Gln Phe TyrAla 420 425 430 Gln Cys Arg Arg Trp Leu Ser Ala Gly Phe His Leu Asp ProArg Val 435 440 445 Leu Val Phe Asp Glu Ser Val Pro Cys Arg Cys Arg ThrPhe Leu Lys 450 455 460 Lys Val Ala Gly Lys Phe Cys Cys Phe Met Arg TrpLeu Gly Gln Glu 465 470 475 480 Cys Thr Cys Phe Leu Glu Pro Ala Glu GlyLeu Val Gly Asp Gln Gly 485 490 495 His Asp Asn Glu Ala Tyr Glu Gly SerGlu Val Asp Pro Ala Glu Pro 500 505 510 Ala His Leu Asp Val Ser Gly ThrTyr Ala Val His Gly His Gln Leu 515 520 525 Glu Ala Leu Tyr Arg Ala LeuAsn Val Pro His Asp Ile Ala Ala Arg 530 535 540 Ala Ser Arg Leu Thr AlaThr Val Glu Leu Val Ala Ser Pro Asp Arg 545 550 555 560 Leu Glu Cys ArgThr Val Leu Gly Asn Lys Thr Phe Arg Thr Thr Val 565 570 575 Val Asp GlyAla His Leu Glu Ala Asn Gly Pro Glu Gln Tyr Val Leu 580 585 590 Ser PheAsp Ala Ser Arg Gln Ser Met Gly Ala Gly Ser His Ser Leu 595 600 605 ThrTyr Glu Leu Thr Pro Ala Gly Leu Gln Val Arg Ile Ser Ser Asn 610 615 620Gly Leu Asp Cys Thr Ala Val Phe Pro Pro Gly Gly Ala Pro Ser Ala 625 630635 640 Ala Pro Gly Glu Val Ala Ala Phe Cys Ser Ala Leu Tyr Arg Tyr Asn645 650 655 Arg Phe Thr Gln Arg His Ser Leu Thr Gly Gly Leu Trp Leu HisPro 660 665 670 Glu Gly Leu Leu Gly Ile Phe Pro Pro Phe Ser Pro Gly HisIle Trp 675 680 685 Glu Ser Ala Asn Pro Phe Cys Gly Glu Gly Thr Leu TyrThr Arg Thr 690 695 700 Trp Ser Thr Ser Gly Phe Ser Ser Asp Phe Ser ProPro Glu Ala Ala 705 710 715 720 Ala Pro Val Pro Ala Ala Ala Pro Gly LeuPro His Pro Thr Pro Pro 725 730 735 Val Ser Asp Ile Trp Val Leu Pro ProPro Ser Glu Gly Ser Gln Ile 740 745 750 Asp Ala Ala Pro Val Pro Pro ValPro Lys Thr Val Gly Leu Pro Ser 755 760 765 Pro Ile Val Leu Ala Pro ProPro Pro Phe Pro Ser Pro Val Arg Lys 770 775 780 Pro Ser Ser Pro Pro ProSer Arg Thr Arg Arg Leu Leu Tyr Thr Tyr 785 790 795 800 Pro Asp Gly AlaArg Val Tyr Ala Gly Ser Leu Phe Glu Ser Asp Cys 805 810 815 Asp Trp LeuVal Asn Ala Ser Asn Pro Gly His Arg Pro Gly Gly Gly 820 825 830 Leu CysHis Ala Phe Tyr Gln Arg Phe Pro Glu Ala Phe Tyr Pro Thr 835 840 845 GluPhe Ile Met Arg Glu Gly Leu Ala Ala Tyr Thr Leu Thr Pro Arg 850 855 860Pro Ile Ile His Ala Val Ala Pro Asp Tyr Arg Val Glu Gln Asn Pro 865 870875 880 Lys Arg Leu Glu Ala Ala Tyr Arg Glu Thr Cys Ser Arg Arg Gly Thr885 890 895 Ala Ala Tyr Pro Leu Leu Gly Ser Gly Ile Tyr Gln Val Pro ValSer 900 905 910 Leu Ser Phe Asp Ala Trp Glu Arg Asn His Arg Pro Gly AspGlu Leu 915 920 925 Tyr Leu Thr Glu Pro Ala Ala Ala Trp Phe Glu Ala AsnLys Pro Ser 930 935 940 Gln Pro Ala Leu Thr Ile Thr Glu Asp Thr Ala ArgThr Ala Asn Leu 945 950 955 960 Ala Leu Glu Ile Asp Ala Ala Thr Glu ValGly Arg Ala Cys Ala Gly 965 970 975 Cys Thr Ile Ser Pro Gly Ile Val HisTyr Gln Phe Thr Ala Gly Val 980 985 990 Pro Gly Ser Gly Lys Ser Arg SerIle Gln Gln Gly Asp Val Asp Val 995 1000 1005 Val Val Val Pro Thr ArgGlu Leu Arg Asn Ser Trp Arg Arg Arg Gly 1010 1015 1020 Phe Ala Ala PheThr Pro His Thr Ala Ala Arg Val Thr Ile Gly Arg 1025 1030 1035 1040 ArgVal Val Ile Asp Glu Ala Pro Ser Leu Pro Pro His Leu Leu Leu 1045 10501055 Leu His Met Gln Arg Ala Ser Ser Val His Leu Leu Gly Asp Pro Asn1060 1065 1070 Gln Ile Pro Ala Ile Asp Phe Glu His Ala Gly Leu Val ProAla Ile 1075 1080 1085 Arg Pro Glu Leu Ala Pro Thr Ser Trp Trp His ValThr His Arg Cys 1090 1095 1100 Pro Ala Asp Val Cys Glu Leu Ile Arg GlyAla Tyr Pro Lys Ile Gln 1105 1110 1115 1120 Thr Thr Ser Arg Val Leu ArgSer Leu Phe Trp Asn Glu Pro Ala Ile 1125 1130 1135 Gly Gln Lys Leu ValPhe Thr Gln Ala Ala Lys Ala Ala Asn Pro Gly 1140 1145 1150 Ala Ile ThrVal His Glu Ala Gln Gly Ala Thr Phe Thr Glu Thr Thr 1155 1160 1165 IleIle Ala Thr Ala Asp Ala Arg Gly Leu Ile Gln Ser Ser Arg Ala 1170 11751180 His Ala Ile Val Ala Leu Thr Arg His Thr Glu Lys Cys Val Ile Leu1185 1190 1195 1200 Asp Ala Pro Gly Leu Leu Arg Glu Val Gly Ile Ser AspVal Ile Val 1205 1210 1215 Asn Asn Phe Phe Leu Ala Gly Gly Glu Val GlyHis His Arg Pro Ser 1220 1225 1230 Val Ile Pro Arg Gly Asn Pro Asp GlnAsn Leu Gly Thr Leu Gln Ala 1235 1240 1245 Phe Pro Pro Ser Cys Gln IleSer Ala Tyr His Gln Leu Ala Glu Glu 1250 1255 1260 Leu Gly His Arg ProAla Pro Val Ala Ala Val Leu Pro Pro Cys Pro 1265 1270 1275 1280 Glu LeuGlu Gln Gly Leu Leu Tyr Met Pro Gln Glu Leu Thr Val Ser 1285 1290 1295Asp Ser Val Leu Val Phe Glu Leu Thr Asp Ile Val His Cys Arg Met 13001305 1310 Ala Ala Pro Ser Gln Arg Lys Ala Val Leu Ser Thr Leu Val GlyArg 1315 1320 1325 Tyr Gly Arg Arg Thr Lys Leu Tyr Glu Ala Ala His SerAsp Val Arg 1330 1335 1340 Glu Ser Leu Ala Arg Phe Ile Pro Thr Ile GlyPro Val Gln Ala Thr 1345 1350 1355 1360 Thr Cys Glu Leu Tyr Glu Leu ValGlu Ala Met Val Glu Lys Gly Gln 1365 1370 1375 Asp Gly Ser Ala Val LeuGlu Leu Asp Leu Cys Asn Arg Asp Val Ser 1380 1385 1390 Arg Ile Thr PhePhe Gln Lys Asp Cys Asn Lys Phe Thr Thr Gly Glu 1395 1400 1405 Thr IleAla His Gly Lys Val Gly Gln Gly Ile Ser Ala Trp Ser Lys 1410 1415 1420Thr Phe Cys Ala Leu Phe Gly Pro Trp Phe Arg Ala Ile Glu Lys Glu 14251430 1435 1440 Ile Leu Ala Leu Leu Pro Pro Asn Ile Phe Tyr Gly Asp AlaTyr Glu 1445 1450 1455 Glu Ser Val Phe Ala Ala Ala Val Ser Gly Ala GlySer Cys Met Val 1460 1465 1470 Phe Glu Asn Asp Phe Ser Glu Phe Asp SerThr Gln Asn Asn Phe Ser 1475 1480 1485 Leu Gly Leu Glu Cys Val Val MetGlu Glu Cys Gly Met Pro Gln Trp 1490 1495 1500 Leu Ile Arg Leu Tyr HisLeu Val Arg Ser Ala Trp Ile Leu Gln Ala 1505 1510 1515 1520 Pro Lys GluSer Leu Lys Gly Phe Trp Lys Lys His Ser Gly Glu Pro 1525 1530 1535 GlyThr Leu Leu Trp Asn Thr Val Trp Asn Met Ala Ile Ile Ala His 1540 15451550 Cys Tyr Glu Phe Arg Asp Phe Arg Val Ala Ala Phe Lys Gly Asp Asp1555 1560 1565 Ser Val Val Leu Cys Ser Asp Tyr Arg Gln Ser Arg Asn AlaAla Ala 1570 1575 1580 Leu Ile Ala Gly Cys Gly Leu Lys Leu Lys Val AspTyr Arg Pro Ile 1585 1590 1595 1600 Gly Leu Tyr Ala Gly Val Val Val AlaPro Gly Leu Gly Thr Leu Pro 1605 1610 1615 Asp Val Val Arg Phe Ala GlyArg Leu Ser Glu Lys Asn Trp Gly Pro 1620 1625 1630 Gly Pro Glu Arg AlaGlu Gln Leu Arg Leu Ala Val Cys Asp Phe Leu 1635 1640 1645 Arg Gly LeuThr Asn Val Ala Gln Val Cys Val Asp Val Val Ser Arg 1650 1655 1660 ValTyr Gly Val Ser Pro Gly Leu Val His Asn Leu Ile Gly Met Leu 1665 16701675 1680 Gln Thr Ile Ala Asp Gly Lys Ala His Phe Thr Glu Thr Ile LysPro 1685 1690 1695 Val Leu Asp Leu Thr Asn Ser Ile Ile Gln Arg Glu Glu1700 1705 53 660 PRT Hepatitis E Virus JMY-Haw (ORF2) 53 Met Arg Pro ArgAla Val Leu Leu Leu Phe Leu Val Leu Leu Pro Met 1 5 10 15 Leu Pro AlaPro Pro Ala Gly Gln Pro Ser Gly Arg Arg Arg Gly Arg 20 25 30 Arg Ser GlyGly Thr Gly Gly Gly Phe Trp Gly Asp Arg Val Asp Ser 35 40 45 Gln Pro PheAla Leu Pro Tyr Ile His Pro Thr Asn Pro Phe Ala Ala 50 55 60 Asp Val ValSer Gln Pro Gly Ala Gly Ala Arg Pro Arg Gln Pro Pro 65 70 75 80 Arg ProLeu Gly Ser Ala Trp Arg Asp Gln Ser Gln Arg Pro Ser Ala 85 90 95 Ala ProArg Arg Arg Ser Ala Pro Ala Gly Ala Ala Pro Leu Thr Ala 100 105 110 ValSer Pro Ala Pro Asp Thr Ala Pro Val Pro Asp Val Asp Ser Arg 115 120 125Gly Ala Ile Leu Arg Arg Gln Tyr Asn Leu Ser Thr Ser Pro Leu Thr 130 135140 Ser Ser Val Ala Ser Gly Thr Asn Leu Val Leu Tyr Ala Ala Pro Leu 145150 155 160 Asn Pro Leu Leu Pro Leu Gln Asp Gly Thr Asn Thr His Ile MetAla 165 170 175 Thr Glu Ala Ser Asn Tyr Ala Gln Tyr Arg Val Val Arg AlaThr Ile 180 185 190 Arg Tyr Arg Pro Leu Val Pro Asn Ala Val Gly Gly TyrAla Ile Ser 195 200 205 Ile Ser Phe Trp Pro Gln Thr Thr Thr Thr Pro ThrSer Val Asp Met 210 215 220 Asn Ser Ile Thr Ser Thr Asp Val Arg Ile LeuVal Gln Pro Gly Ile 225 230 235 240 Ala Ser Glu Leu Val Ile Pro Ser GluArg Leu His Tyr Arg Asn Gln 245 250 255 Gly Trp Arg Ser Val Glu Thr ThrGly Val Ala Glu Glu Glu Ala Thr 260 265 270 Ser Gly Leu Val Met Leu CysIle His Gly Ser Pro Val Asn Ser Tyr 275 280 285 Thr Asn Thr Pro Tyr ThrGly Ala Leu Gly Leu Leu Asp Phe Ala Leu 290 295 300 Glu Leu Glu Phe ArgAsn Leu Thr Pro Gly Asn Thr Asn Thr Arg Val 305 310 315 320 Ser Arg TyrThr Ser Thr Ala Arg His Arg Leu Arg Arg Gly Ala Asp 325 330 335 Gly ThrAla Glu Leu Thr Thr Thr Ala Ala Thr Arg Phe Met Lys Asp 340 345 350 LeuHis Phe Thr Gly Thr Asn Gly Val Gly Glu Val Gly Arg Gly Ile 355 360 365Ala Leu Thr Leu Phe Asn Leu Ala Asp Thr Leu Leu Gly Gly Leu Pro 370 375380 Thr Glu Leu Ile Ser Ser Ala Gly Gly Gln Leu Phe Tyr Ser Arg Pro 385390 395 400 Val Val Ser Ala Asn Gly Glu Pro Thr Val Lys Leu Tyr Thr SerVal 405 410 415 Glu Asn Ala Gln Gln Asp Lys Gly Ile Thr Ile Pro His AspIle Asp 420 425 430 Leu Gly Asp Ser Arg Val Val Ile Gln Asp Tyr Asp AsnGln His Glu 435 440 445 Gln Asp Arg Pro Thr Pro Ser Pro Ala Pro Ser ArgPro Phe Ser Val 450 455 460 Leu Arg Ala Asn Asp Val Leu Trp Leu Ser LeuThr Ala Ala Glu Tyr 465 470 475 480 Asp Gln Thr Thr Tyr Gly Ser Ser ThrAsn Pro Met Tyr Val Ser Asp 485 490 495 Thr Val Thr Leu Val Asn Val AlaThr Gly Ala Gln Ala Val Ala Arg 500 505 510 Ser Leu Asp Trp Ser Lys ValThr Leu Asp Gly Arg Pro Leu Thr Thr 515 520 525 Ile Gln Gln Tyr Ser LysThr Phe Tyr Val Leu Pro Leu Arg Gly Lys 530 535 540 Leu Ser Phe Trp GluAla Gly Thr Thr Lys Ala Gly Tyr Pro Tyr Asn 545 550 555 560 Tyr Asn ThrThr Ala Ser Asp Gln Ile Leu Ile Glu Asn Ala Ala Gly 565 570 575 His ArgVal Ala Ile Ser Thr Tyr Thr Thr Ser Leu Gly Ala Gly Pro 580 585 590 ThrSer Ile Ser Ala Val Gly Val Leu Ala Pro His Ser Ala Leu Ala 595 600 605Ala Leu Glu Asp Thr Val Asp Tyr Pro Ala Arg Ala His Thr Phe Asp 610 615620 Asp Phe Cys Pro Glu Cys Arg Thr Leu Gly Leu Gln Gly Cys Ala Phe 625630 635 640 Gln Ser Thr Ile Ala Glu Leu Gln Arg Leu Lys Met Lys Val GlyLys 645 650 655 Thr Arg Glu Ser 660 54 1707 PRT Hepatitis E VirusJKK-Sap (ORF1) 54 Met Glu Ala His Gln Phe Ile Lys Ala Pro Gly Val ThrThr Ala Ile 1 5 10 15 Glu Gln Ala Ala Leu Ala Ala Ala Asn Ser Ala LeuAla Asn Ala Val 20 25 30 Val Val Arg Pro Phe Leu Ser Arg Leu Gln Thr GluIle Leu Ile Asn 35 40 45 Leu Met Gln Pro Arg Gln Leu Val Phe Arg Pro GluVal Leu Trp Asn 50 55 60 His Pro Ile Gln Arg Val Ile His Asn Glu Leu GluGln Tyr Cys Arg 65 70 75 80 Ala Arg Ala Gly Arg Cys Leu Glu Val Gly AlaHis Pro Arg Ser Ile 85 90 95 Asn Asp Asn Pro Asn Val Leu His Arg Cys PheLeu Lys Pro Val Gly 100 105 110 Arg Asp Val Gln Arg Trp Tyr Thr Ala ProThr Arg Gly Pro Ala Ala 115 120 125 Asn Cys Arg Arg Ser Ala Leu Arg GlyLeu Pro Pro Ala Asp Arg Thr 130 135 140 Tyr Cys Phe Asn Gly Phe Ser GlyCys Thr Phe Ala Ala Glu Thr Gly 145 150 155 160 Ile Ala Leu Tyr Ser LeuHis Asp Leu Trp Pro Ala Asp Val Ala Glu 165 170 175 Ala Met Ala Arg HisGly Met Thr Arg Leu Tyr Ala Ala Leu His Leu 180 185 190 Pro Pro Glu ValLeu Leu Pro Pro Gly Thr Tyr His Thr Thr Ser Tyr 195 200 205 Leu Leu IleHis Asp Gly Asp Arg Ala Val Ile Thr Tyr Glu Gly Asp 210 215 220 Ser SerAla Gly Tyr Asn His Asp Val Ser Ile Leu Arg Ala Trp Ile 225 230 235 240Arg Thr Thr Lys Val Thr Gly Asp His Pro Leu Val Ile Glu Arg Val 245 250255 Arg Ala Val Gly Cys His Phe Val Leu Leu Leu Thr Ala Ala Pro Glu 260265 270 Pro Ser Pro Met Pro Tyr Val Pro Tyr Pro Arg Ser Thr Glu Val Tyr275 280 285 Val Arg Ser Ile Phe Gly Pro Gly Gly Ser Pro Ser Leu Phe ProThr 290 295 300 Ala Cys Ser Thr Lys Ser Thr Phe His Ala Val Pro Val HisIle Trp 305 310 315 320 Asp Arg Leu Met Leu Phe Gly Ala Thr Leu Asp AspGln Ala Phe Cys 325 330 335 Cys Ser Arg Leu Met Thr Tyr Leu Arg Gly IleSer Tyr Lys Val Thr 340 345 350 Val Gly Ala Leu Val Ala Asn Glu Gly TrpAsn Ala Ser Glu Asp Ala 355 360 365 Leu Thr Ala Val Ile Thr Ala Ala TyrLeu Thr Ile Cys His Gln Arg 370 375 380 Tyr Leu Arg Thr Gln Ala Ile SerLys Gly Met Lys Arg Leu Glu Leu 385 390 395 400 Glu His Ala Gln Lys PheIle Thr Arg Leu Tyr Ser Trp Leu Phe Glu 405 410 415 Lys Ser Gly Arg AspTyr Ile Pro Gly Arg Gln Leu Gln Phe Tyr Ala 420 425 430 Gln Cys Arg ArgTrp Leu Ser Ala Gly Phe His Leu Asp Pro Arg Val 435 440 445 Leu Val PheAsp Glu Ala Ala Pro Cys Arg Cys Arg Ser Leu Leu Arg 450 455 460 Lys AlaAla His Lys Phe Cys Cys Phe Met Arg Trp Leu Gly Gln Asp 465 470 475 480Cys Thr Cys Phe Leu Gln Pro Val Glu Gly Arg Val Gly Glu Gln Gly 485 490495 Tyr Asp Asn Glu Ala Phe Glu Gly Ser Asp Val Asp Pro Ala Glu Glu 500505 510 Ala Thr Val Ser Ile Ser Gly Ser Tyr Ile Val Thr Gly Ser Gln Leu515 520 525 Gln Pro Leu Tyr Gln Ala Leu Gly Ile Pro Ser Asp Leu Ala AlaArg 530 535 540 Ala Gly Arg Leu Thr Ala Thr Val Glu Val Ser Asp Thr AspGly Arg 545 550 555 560 Leu Thr Cys Lys Thr Thr Met Gly Asn Lys Thr PheThr Thr Val Phe 565 570 575 Thr Asp Gly Ala Gln Leu Glu Ala Asn Gly ProGlu Gln Tyr Val Leu 580 585 590 Ser Phe Asp Leu Ala Lys Gln Thr Met AlaAla Gly Pro His Ser Leu 595 600 605 Ser Tyr Ala Leu Thr Pro Ala Gly LeuGlu Val Arg Val Val Ser Ala 610 615 620 Gly Leu Asp Cys Arg Ala Val PhePro Ser Gly Val Ala Thr Pro Ser 625 630 635 640 Ala Ser Gly Glu Val SerAla Phe Cys Ser Ala Leu Tyr Arg Phe Asn 645 650 655 Arg Cys Val Gln ArgHis Ser Leu Ile Gly Gly Leu Trp Tyr Tyr Pro 660 665 670 Glu Gly Leu IleGly Leu Phe Pro Pro Phe Ala Pro Gly His Thr Trp 675 680 685 Glu Ser AlaAsn Pro Phe Cys Gly Glu Ser Thr Leu Tyr Thr Arg Thr 690 695 700 Trp SerVal Ser Gly Phe Ser Ser Cys Phe Ser Pro Phe Glu Pro Pro 705 710 715 720Ala Leu Asp Ser Pro Pro Pro Ala Glu Ala Asp Thr Pro Met Ala Val 725 730735 Asp Val Pro Pro Pro Ala Thr Leu Thr Leu Pro Gln Pro Pro Ala Pro 740745 750 Glu Arg Ala Val Pro Pro Gln Asp Leu Ala Asp Gly Asp Val Ala Arg755 760 765 Ala Ser Pro Gly Val Ser Ala Ala Pro Pro Val Pro Ala Gln SerVal 770 775 780 Thr Asp Pro Pro Val Ser Arg Arg Arg Leu Leu His Thr TyrPro Asp 785 790 795 800 Gly Ser Lys Val Tyr Ala Gly Ser Leu Phe Glu SerGlu Cys Thr Trp 805 810 815 Leu Val Asn Ala Ser Asn Pro Gly His Arg ProGly Gly Gly Leu Cys 820 825 830 His Ala Phe Tyr Gln Arg Phe Pro Glu SerPhe Asp Pro Ala Glu Phe 835 840 845 Val Met Ser Asp Gly Phe Ala Ala TyrThr Leu Thr Pro Arg Pro Ile 850 855 860 Ile His Ala Val Ala Pro Asp TyrArg Val Glu His Asn Pro Lys Arg 865 870 875 880 Leu Glu Ala Ala Tyr ArgGlu Thr Cys Ser Arg Arg Gly Thr Ala Ala 885 890 895 Tyr Pro Leu Leu GlyAla Gly Ile Tyr Lys Val Pro Val Gly Leu Ser 900 905 910 Phe Asp Ala TrpGlu Arg Asn His Arg Pro Gly Asp Glu Leu Tyr Leu 915 920 925 Thr Glu ProAla Ile Ala Trp Phe Glu Ala Asn Arg Pro Thr Leu Pro 930 935 940 Ala LeuThr Ile Thr Glu Asp Thr Ala Arg Thr Ala Asn Leu Ala Leu 945 950 955 960Glu Leu Asp Ser Ala Thr Glu Val Gly Arg Ala Cys Ala Gly Cys Arg 965 970975 Val Glu Pro Gly Val Val His Tyr Gln Phe Thr Ala Gly Val Pro Gly 980985 990 Ser Gly Lys Ser Arg Ser Ile Gln Gln Gly Glu Val Asp Val Val Val995 1000 1005 Val Pro Thr Arg Glu Leu Arg Asn Ser Trp Arg Arg Arg GlyPhe Ala 1010 1015 1020 Ala Tyr Thr Pro His Thr Ala Ala Arg Val Thr ArgGly Arg Arg Val 1025 1030 1035 1040 Val Ile Asp Glu Ala Pro Ser Leu ProPro His Leu Leu Leu Leu His 1045 1050 1055 Met Gln Arg Ala Ser Ser ValHis Leu Leu Gly Asp Pro Asn Gln Ile 1060 1065 1070 Pro Ala Ile Asp PheGlu His Ala Gly Leu Val Pro Ala Ile Arg Pro 1075 1080 1085 Glu Leu ValPro Thr Lys Trp Trp His Leu Thr His Arg Cys Pro Ala 1090 1095 1100 AspVal Cys Glu Leu Ile Arg Gly Ala Tyr Pro Lys Ile Gln Thr Ala 1105 11101115 1120 Ser Arg Val Phe Arg Ser Leu Phe Trp Gly Glu Pro Pro Val GlyGln 1125 1130 1135 Lys Leu Val Phe Thr Gln Ala Ala Lys Ala Ala Asn ProGly Ala Ile 1140 1145 1150 Thr Val His Glu Ala Gln Gly Ala Thr Phe ThrGlu Thr Thr Ile Ile 1155 1160 1165 Ala Thr Ala Asp Ala Arg Gly Leu IleGln Ser Ser Arg Ala His Ala 1170 1175 1180 Ile Val Ala Leu Thr Arg HisThr Glu Lys Cys Val Val Val Asp Ala 1185 1190 1195 1200 Pro Gly Leu LeuArg Glu Val Gly Ile Ser Asp Ala Ile Val Asn Asn 1205 1210 1215 Phe PheLeu Ser Gly Gly Gln Ile Gly Gln His Arg Pro Ser Val Ile 1220 1225 1230Pro Arg Gly Thr Ile Asn Asn Asn Val Asp Thr Leu Asp Ala Phe Pro 12351240 1245 Pro Ser Cys Gln Phe Ser Ala Tyr His Gln Leu Ala Glu Glu LeuGly 1250 1255 1260 His Arg Pro Ala Pro Ile Ala Ala Val Leu Pro Pro CysPro Glu Leu 1265 1270 1275 1280 Glu Gln Gly Leu Leu Tyr Met Pro Gln GluLeu Thr Thr Ser Asp Ser 1285 1290 1295 Val Leu Thr Phe Glu Leu Thr AspIle Val His Cys Arg Met Ala Ala 1300 1305 1310 Pro Ser Gln Arg Lys AlaVal Leu Ser Thr Leu Val Gly Arg Tyr Gly 1315 1320 1325 Arg Arg Thr LysLeu Tyr Glu Ala Ala His Ala Asp Val Arg Gly Ser 1330 1335 1340 Leu AsnHis Phe Ile Pro Glu Leu Gly Pro Val Ser Val Thr Thr Cys 1345 1350 13551360 Glu Leu Tyr Glu Leu Val Glu Ala Met Val Glu Lys Gly Gln Asp Gly1365 1370 1375 Ser Ala Val Leu Glu Leu Asp Leu Cys Ser Arg Asp Val SerArg Ile 1380 1385 1390 Thr Phe Phe Gln Lys Asp Cys Asn Lys Phe Thr ThrGly Glu Thr Ile 1395 1400 1405 Ala His Gly Lys Val Gly Gln Gly Ile SerAla Trp Ser Lys Thr Phe 1410 1415 1420 Cys Ala Leu Phe Gly Pro Trp PheArg Ala Ile Glu Lys Glu Ile Leu 1425 1430 1435 1440 Ala Val Leu Ala ProAsn Val Phe Tyr Gly Asp Ala Tyr Glu Asp Thr 1445 1450 1455 Val Leu AlaAla Ala Val Ala Gly Ala Pro Gly Cys Lys Val Phe Glu 1460 1465 1470 AsnAsp Phe Ser Glu Phe Asp Ser Thr Gln Asn Asn Phe Ser Leu Gly 1475 14801485 Leu Glu Cys Ile Ile Met Glu Glu Cys Gly Met Pro Gln Trp Met Ile1490 1495 1500 Arg Leu Tyr His Leu Val Arg Ser Ala Trp Val Leu Gln AlaPro Lys 1505 1510 1515 1520 Glu Ser Leu Arg Gly Phe Trp Lys Lys His SerGly Glu Pro Gly Thr 1525 1530 1535 Leu Leu Trp Asn Thr Val Trp Asn MetAla Val Ile Ala His Cys Tyr 1540 1545 1550 Glu Phe Arg Asp Leu Lys ValAla Ala Phe Lys Gly Asp Asp Ser Val 1555 1560 1565 Val Leu Cys Ser AspTyr Arg Gln Ser Arg Asp Ala Ala Ala Leu Ile 1570 1575 1580 Ala Gly CysGly Leu Lys Leu Lys Val Asp Phe Arg Pro Ile Gly Leu 1585 1590 1595 1600Tyr Ala Gly Val Val Val Ala Pro Gly Leu Gly Thr Leu Pro Asp Val 16051610 1615 Val Arg Phe Ala Gly Arg Leu Ser Glu Lys Asn Trp Gly Pro GlySer 1620 1625 1630 Glu Arg Ala Glu Gln Leu Arg Leu Ala Val Cys Asp PheLeu Arg Lys 1635 1640 1645 Leu Thr Asn Val Ala Gln Val Cys Val Asp ValVal Ser Gln Val Tyr 1650 1655 1660 Gly Val Ser Pro Gly Leu Val His AsnLeu Ile Gly Met Leu Gln Thr 1665 1670 1675 1680 Ile Ala Asp Gly Lys AlaHis Phe Thr Glu Thr Val Lys Pro Val Leu 1685 1690 1695 Asp Leu Thr AsnSer Ile Ile His Arg Val Glu 1700 1705 55 674 PRT Hepatitis E VirusJKK-Sap (ORF2) 55 Met Asn Asn Met Phe Phe Cys Ser Val His Gly Asp AlaThr Met Arg 1 5 10 15 Ser Arg Ala Phe Leu Phe Leu Phe Leu Val Leu LeuPro Met Leu Pro 20 25 30 Ala Pro Pro Ala Gly Gln Pro Ser Gly Arg Arg ArgGly Arg Arg Ser 35 40 45 Gly Gly Ala Gly Gly Gly Phe Trp Gly Asp Arg ValAsp Ser Gln Pro 50 55 60 Phe Ala Leu Pro Tyr Ile His Pro Thr Asn Pro PheAla Ser Asp Ile 65 70 75 80 Pro Ala Ala Ala Gly Ala Gly Ala Arg Pro ArgGln Pro Ala Arg Pro 85 90 95 Leu Gly Ser Ala Trp Arg Asp Gln Ser Gln ArgPro Ala Thr Ser Ala 100 105 110 Arg Arg Arg Ser Ala Pro Ala Gly Ala SerPro Leu Thr Ala Val Ala 115 120 125 Pro Ala Pro Asp Thr Ala Pro Val ProAsp Val Asp Ser Arg Gly Ala 130 135 140 Ile Leu Arg Arg Gln Tyr Asn LeuSer Thr Ser Pro Leu Thr Ser Thr 145 150 155 160 Ile Ala Thr Gly Thr AsnLeu Val Leu Tyr Ala Ala Pro Leu Ser Pro 165 170 175 Leu Leu Pro Leu GlnAsp Gly Thr Asn Thr His Ile Met Ala Thr Glu 180 185 190 Ala Ser Asn TyrAla Gln Tyr Arg Val Val Arg Ala Thr Ile Arg Tyr 195 200 205 Arg Pro LeuVal Pro Asn Ala Val Gly Gly Tyr Ala Ile Ser Ile Ser 210 215 220 Phe TrpPro Gln Thr Thr Thr Thr Pro Thr Ser Val Asp Met Asn Ser 225 230 235 240Ile Thr Ser Thr Asp Val Arg Ile Leu Val Gln Pro Gly Ile Ala Ser 245 250255 Glu Leu Val Ile Pro Ser Glu Arg Leu His Tyr Arg Asn Gln Gly Trp 260265 270 Arg Ser Val Glu Thr Ser Gly Val Ala Glu Glu Glu Ala Thr Ser Gly275 280 285 Leu Val Met Leu Cys Ile His Gly Ser Pro Val Asn Ser Tyr ThrAsn 290 295 300 Thr Pro Tyr Thr Gly Ala Leu Gly Leu Leu Asp Phe Ala LeuGlu Leu 305 310 315 320 Glu Phe Arg Asn Leu Thr Pro Gly Asn Thr Asn ThrArg Val Ser Arg 325 330 335 Tyr Ser Ser Ser Ala Arg His Lys Leu Arg ArgGly Pro Asp Gly Thr 340 345 350 Ala Glu Leu Thr Thr Thr Ala Ala Thr ArgPhe Met Lys Asp Leu His 355 360 365 Phe Thr Gly Thr Asn Gly Val Gly GluVal Gly Arg Gly Ile Ala Leu 370 375 380 Thr Leu Phe Asn Leu Ala Asp ThrLeu Leu Gly Gly Leu Pro Thr Glu 385 390 395 400 Leu Ile Ser Ser Ala GlyGly Gln Leu Phe Tyr Ser Arg Pro Val Val 405 410 415 Ser Ala Asn Gly GluPro Thr Val Lys Leu Tyr Thr Ser Val Glu Asn 420 425 430 Ala Gln Gln AspLys Gly Ile Ala Ile Pro His Asp Ile Asp Leu Gly 435 440 445 Glu Ser ArgVal Val Ile Gln Asp Tyr Asp Asn Gln His Glu Gln Asp 450 455 460 Arg ProThr Pro Ser Pro Ala Pro Ser Arg Pro Phe Ser Val Leu Arg 465 470 475 480Ala Asn Asp Val Leu Trp Leu Ser Leu Thr Ala Ala Glu Tyr Asp Gln 485 490495 Thr Thr Tyr Gly Ser Ser Thr Asn Pro Met Tyr Val Ser Asp Thr Val 500505 510 Thr Phe Val Asn Val Ala Thr Gly Ala Gln Gly Val Ser Arg Ser Leu515 520 525 Asp Trp Ser Lys Val Thr Leu Asp Gly Arg Pro Leu Met Thr IleGln 530 535 540 Gln Tyr Ser Lys Thr Phe Phe Val Leu Pro Leu Arg Gly LysLeu Ser 545 550 555 560 Phe Trp Glu Ala Gly Thr Thr Lys Ala Gly Tyr ProTyr Asn Tyr Asn 565 570 575 Thr Thr Ala Ser Asp Gln Ile Leu Ile Glu AsnAla Ala Gly His Arg 580 585 590 Val Cys Ile Ser Thr Tyr Thr Thr Asn LeuGly Ser Gly Pro Val Ser 595 600 605 Ile Ser Ala Val Gly Val Leu Ala ProHis Ser Ala Leu Ala Ala Leu 610 615 620 Glu Asp Thr Val Asp Tyr Pro AlaArg Ala His Thr Phe Asp Asp Phe 625 630 635 640 Cys Pro Glu Cys Arg AlaLeu Gly Leu Gln Gly Cys Ala Phe Gln Ser 645 650 655 Thr Val Ala Glu LeuGln Arg Leu Lys Met Lys Val Gly Lys Thr Arg 660 665 670 Glu Tyr 56 1707PRT Hepatitis E Virus JAK-Sai (ORF1) 56 Met Glu Ala His Gln Phe Ile LysAla Pro Gly Val Thr Thr Ala Ile 1 5 10 15 Glu Gln Ala Ala Leu Ala AlaAla Asn Ser Ala Leu Ala Asn Ala Val 20 25 30 Val Val Arg Pro Phe Leu SerArg Leu Gln Thr Glu Ile Leu Ile Asn 35 40 45 Leu Met Gln Pro Arg Gln LeuVal Phe Arg Pro Glu Val Leu Trp Asn 50 55 60 His Pro Ile Gln Arg Val IleHis Asn Glu Leu Glu Gln Tyr Cys Arg 65 70 75 80 Ala Arg Ala Gly Arg CysLeu Glu Val Gly Ala His Pro Arg Ser Ile 85 90 95 Asn Asp Asn Pro Asn ValLeu His Arg Cys Phe Leu Lys Pro Val Gly 100 105 110 Arg Asp Val Gln ArgTrp Tyr Thr Ala Pro Thr Arg Gly Pro Ala Ala 115 120 125 Asn Cys Arg ArgSer Ala Leu Arg Gly Leu Pro Pro Ala Asp Arg Thr 130 135 140 Tyr Cys PheAsp Gly Phe Ser Gly Cys Thr Phe Ala Ala Glu Thr Gly 145 150 155 160 ValAla Leu Tyr Ser Leu His Asp Leu Trp Pro Ala Asp Val Ala Glu 165 170 175Ala Met Ala Arg His Gly Met Thr Arg Leu Tyr Ala Ala Leu His Leu 180 185190 Pro Pro Glu Val Leu Leu Pro Pro Gly Thr Tyr His Thr Thr Ser Tyr 195200 205 Leu Leu Ile His Asp Gly Asp Arg Ala Val Ile Thr Tyr Glu Gly Asp210 215 220 Ser Ser Ala Gly Tyr Asn His Asp Val Ser Ile Leu Arg Ala TrpIle 225 230 235 240 Arg Thr Thr Lys Val Thr Gly Asp His Pro Leu Val IleGlu Arg Val 245 250 255 Arg Ala Val Gly Cys His Phe Val Leu Leu Leu ThrAla Ala Pro Glu 260 265 270 Pro Ser Pro Met Pro Tyr Val Pro Tyr Pro ArgSer Thr Glu Val Tyr 275 280 285 Val Arg Ser Ile Phe Gly Pro Gly Gly SerPro Ser Leu Phe Pro Ser 290 295 300 Ala Cys Ser Thr Lys Ser Thr Phe HisAla Val Pro Val His Ile Trp 305 310 315 320 Asp Arg Leu Met Leu Phe GlyAla Thr Leu Asp Asp Gln Ala Phe Cys 325 330 335 Cys Ser Arg Leu Met ThrTyr Leu Arg Gly Ile Ser Tyr Lys Val Thr 340 345 350 Val Gly Ala Leu ValAla Asn Glu Gly Trp Asn Ala Ser Glu Asp Ala 355 360 365 Leu Thr Ala ValIle Thr Ala Ala Tyr Leu Thr Ile Cys His Gln Arg 370 375 380 Tyr Leu ArgThr Gln Ala Ile Ser Lys Gly Met Lys Arg Leu Glu Leu 385 390 395 400 GluHis Ala Gln Lys Phe Ile Thr Arg Leu Tyr Ser Trp Leu Phe Glu 405 410 415Lys Ser Gly Arg Asp Tyr Ile Pro Gly Arg Gln Leu Gln Phe Tyr Ala 420 425430 Gln Cys Arg Arg Trp Leu Ser Ala Gly Phe His Leu Asp Pro Arg Val 435440 445 Leu Val Phe Asp Glu Ala Ala Pro Cys Arg Cys Arg Ser Leu Leu Arg450 455 460 Lys Ala Ala His Lys Phe Cys Cys Phe Met Arg Trp Leu Gly GlnAsp 465 470 475 480 Cys Thr Cys Phe Leu Gln Pro Ile Glu Gly Arg Val GlyGlu Gln Gly 485 490 495 Tyr Asp Asn Glu Ala Phe Glu Gly Ser Asp Val AspPro Ala Glu Glu 500 505 510 Ala Thr Val Ser Ile Ser Gly Ser Tyr Ile ValThr Gly Ser Gln Leu 515 520 525 Gln Pro Leu Tyr Gln Ala Leu Gly Ile ProSer Asp Leu Ala Ala Arg 530 535 540 Ala Gly Arg Leu Thr Ala Thr Val GluVal Ser Asp Ala Asp Gly Arg 545 550 555 560 Leu Thr Cys Lys Thr Ile MetGly Asn Lys Thr Phe Thr Thr Val Phe 565 570 575 Thr Asp Gly Ala Gln LeuGlu Val Asn Gly Pro Glu Gln Tyr Val Leu 580 585 590 Ser Phe Asp Leu AlaLys Gln Thr Met Ala Ala Gly Pro His Ser Leu 595 600 605 Ser Tyr Val LeuThr Ser Ala Gly Leu Glu Val Arg Val Val Ser Ala 610 615 620 Gly Leu AspCys Lys Ala Val Phe Pro Ser Gly Val Ala Thr Pro Ser 625 630 635 640 AlaSer Gly Glu Val Ser Ala Phe Cys Ser Ala Leu Tyr Arg Phe Asn 645 650 655Arg Cys Val Gln Arg His Ser Leu Ile Gly Gly Leu Trp Tyr Tyr Pro 660 665670 Glu Gly Leu Ile Gly Leu Phe Pro Pro Phe Ala Pro Gly His Thr Trp 675680 685 Glu Ser Thr Asn Pro Phe Cys Gly Glu Ser Thr Leu Tyr Thr Arg Thr690 695 700 Trp Ser Val Ser Gly Phe Ser Ser Cys Phe Ser Pro Leu Glu ProPro 705 710 715 720 Ala Ser Gly Ser Leu Pro Pro Ala Glu Ile Asp Pro ProVal Thr Val 725 730 735 Asp Ala Pro Ser Pro Ser Ile Leu Ala Leu Pro ArgPro Ser Val Phe 740 745 750 Glu Gln Thr Thr Pro Pro Leu Asp Pro Ala GlyAsp Ala Ala Ala Ser 755 760 765 Ala Pro Pro Gly Ala Pro Gly Val Pro ProAla Pro Ala Arg Pro Val 770 775 780 Thr His Pro Ser Gly Pro Arg Arg ArgLeu Leu His Thr Tyr Pro Asp 785 790 795 800 Gly Ser Lys Val Tyr Ala GlySer Leu Phe Glu Ser Glu Cys Thr Trp 805 810 815 Leu Val Asn Ala Ser AsnPro Gly His Arg Pro Gly Gly Gly Leu Cys 820 825 830 His Ala Phe Tyr GlnArg Phe Pro Glu Ser Phe Asp Pro Ala Glu Phe 835 840 845 Val Met Ser AspGly Phe Ala Ala Tyr Thr Leu Thr Pro Arg Pro Ile 850 855 860 Ile His AlaVal Ala Pro Asp Tyr Arg Val Glu His Asn Pro Lys Arg 865 870 875 880 LeuGlu Ala Ala Tyr Arg Glu Thr Cys Ser Arg Arg Gly Thr Ala Ala 885 890 895Tyr Pro Leu Leu Gly Ala Gly Ile Tyr Lys Val Pro Val Gly Leu Ser 900 905910 Phe Asp Ala Trp Glu Arg Asn His Arg Pro Gly Asp Glu Leu Tyr Leu 915920 925 Thr Glu Pro Ala Ile Ala Trp Phe Glu Ala Asn Arg Pro Thr Leu Pro930 935 940 Ala Leu Thr Ile Thr Glu Asp Thr Ala Arg Thr Ala Asn Leu AlaLeu 945 950 955 960 Glu Leu Asp Ser Ala Thr Glu Val Gly Arg Ala Cys AlaGly Cys Arg 965 970 975 Val Glu Pro Gly Val Val His Tyr Gln Phe Thr AlaGly Val Pro Gly 980 985 990 Ser Gly Lys Ser Arg Ser Ile Gln Gln Gly GluVal Asp Val Val Val 995 1000 1005 Val Pro Thr Arg Glu Leu Arg Asn SerTrp Arg Arg Arg Gly Phe Ala 1010 1015 1020 Ala Tyr Thr Pro His Thr AlaAla Arg Val Thr Arg Gly Arg Arg Ile 1025 1030 1035 1040 Val Ile Asp GluAla Pro Ala Leu Pro Pro His Leu Leu Leu Leu His 1045 1050 1055 Met GlnArg Ala Ser Ser Val His Leu Leu Gly Asp Pro Asn Gln Ile 1060 1065 1070Pro Ala Ile Asp Phe Glu His Ala Gly Leu Val Pro Ala Ile Arg Pro 10751080 1085 Glu Leu Val Pro Thr Lys Trp Trp His Leu Thr His Arg Cys ProAla 1090 1095 1100 Asp Val Cys Glu Leu Ile Arg Gly Ala Tyr Pro Lys IleGln Thr Ala 1105 1110 1115 1120 Ser Arg Val Leu Arg Ser Leu Phe Trp GlyGlu Pro Pro Val Gly Gln 1125 1130 1135 Lys Leu Val Phe Thr Gln Ala AlaLys Ala Ala Asn Pro Gly Ala Ile 1140 1145 1150 Thr Val His Glu Ala GlnGly Ala Thr Phe Thr Glu Thr Thr Ile Ile 1155 1160 1165 Ala Thr Ala AspAla Arg Gly Leu Ile Gln Ser Ser Arg Ala His Ala 1170 1175 1180 Ile ValAla Leu Thr Arg His Thr Glu Lys Cys Val Val Val Asp Ala 1185 1190 11951200 Pro Gly Leu Leu Arg Glu Val Gly Ile Ser Asp Ala Ile Val Asn Asn1205 1210 1215 Phe Phe Leu Ser Gly Gly Gln Ile Gly Gln His Arg Pro SerVal Ile 1220 1225 1230 Pro Arg Gly Thr Val Asp Ser Asn Val Asp Thr LeuAsp Ala Phe Pro 1235 1240 1245 Pro Ser Cys Gln Phe Ser Ala Tyr His GlnLeu Ala Glu Glu Leu Gly 1250 1255 1260 His Arg Pro Ala Pro Ile Ala AlaVal Leu Pro Pro Cys Pro Glu Leu 1265 1270 1275 1280 Glu Gln Gly Leu LeuTyr Met Pro Gln Glu Leu Thr Thr Ser Asp Ser 1285 1290 1295 Val Leu ThrPhe Glu Leu Thr Asp Ile Val His Cys Arg Met Ala Ala 1300 1305 1310 ProSer Gln Arg Lys Ala Val Leu Ser Thr Leu Val Gly Arg Tyr Gly 1315 13201325 Arg Arg Thr Lys Leu Tyr Glu Ala Ala His Ala Asp Val Arg Gly Ser1330 1335 1340 Leu Asn His Phe Ile Pro Glu Leu Gly Pro Ile Ser Val ThrThr Cys 1345 1350 1355 1360 Glu Leu Tyr Glu Leu Val Glu Ala Met Val GluLys Gly Gln Asp Gly 1365 1370 1375 Ser Ala Val Leu Glu Leu Asp Leu CysSer Arg Asp Val Ser Arg Ile 1380 1385 1390 Thr Phe Phe Gln Lys Asp CysAsn Lys Phe Thr Thr Gly Glu Thr Ile 1395 1400 1405 Ala His Gly Lys ValGly Gln Gly Ile Ser Ala Trp Ser Lys Thr Phe 1410 1415 1420 Cys Ala LeuPhe Gly Pro Trp Phe Arg Ala Ile Glu Lys Glu Ile Leu 1425 1430 1435 1440Ala Ala Leu Ala Pro Asn Val Phe Tyr Gly Asp Ala Tyr Glu Asp Thr 14451450 1455 Val Leu Ala Ala Ala Val Ala Gly Ala Pro Gly Cys Lys Val PheGlu 1460 1465 1470 Asn Asp Phe Ser Glu Phe Asp Ser Thr Gln Asn Asn PheSer Leu Gly 1475 1480 1485 Leu Glu Cys Ile Ile Met Glu Glu Cys Gly MetPro Gln Trp Met Ile 1490 1495 1500 Arg Leu Tyr His Leu Val Arg Ser AlaTrp Val Leu Gln Ala Pro Lys 1505 1510 1515 1520 Glu Ser Leu Arg Gly PheTrp Lys Lys His Ser Gly Glu Pro Gly Thr 1525 1530 1535 Leu Leu Trp AsnThr Val Trp Asn Met Ala Val Ile Ala His Cys Tyr 1540 1545 1550 Glu PheArg Asp Leu Lys Val Ala Ala Phe Lys Gly Asp Asp Ser Val 1555 1560 1565Val Leu Cys Ser Asp Tyr Arg Gln Ser Arg Asn Ala Ala Ala Leu Ile 15701575 1580 Thr Gly Cys Gly Leu Lys Leu Lys Val Asp Phe Arg Pro Ile GlyLeu 1585 1590 1595 1600 Tyr Ala Gly Val Val Val Ala Pro Gly Leu Gly ThrLeu Pro Asp Val 1605 1610 1615 Val Arg Phe Ala Gly Arg Leu Ser Glu LysAsn Trp Gly Pro Gly Pro 1620 1625 1630 Glu Arg Ala Glu Gln Leu Arg LeuAla Val Cys Asp Phe Leu Arg Lys 1635 1640 1645 Leu Thr Asn Val Ala GlnVal Cys Val Asp Val Val Ser Arg Val Tyr 1650 1655 1660 Gly Val Ser ProGly Leu Val His Asn Leu Ile Gly Met Leu Gln Thr 1665 1670 1675 1680 IleAla Asp Gly Lys Ala His Phe Thr Glu Thr Val Lys Pro Val Leu 1685 16901695 Asp Leu Thr Asn Ser Ile Ile His Arg Val Glu 1700 1705 57 674 PRTHepatitis E Virus JAK-Sai (ORF2) 57 Met Asn Asn Met Phe Phe Cys Ser ValHis Gly Asp Ala Thr Met Arg 1 5 10 15 Ser Arg Ala Leu Leu Phe Leu LeuPhe Val Phe Leu Pro Met Leu Pro 20 25 30 Ala Pro Pro Ala Gly Gln Pro SerGly Arg Arg Arg Gly Arg Arg Ser 35 40 45 Gly Gly Ala Gly Gly Gly Phe TrpGly Asp Arg Val Asp Ser Gln Pro 50 55 60 Phe Ala Leu Pro Tyr Ile His ProThr Asn Pro Phe Ala Ser Asp Ile 65 70 75 80 Pro Thr Ala Ala Gly Ala GlyAla Arg Pro Arg Gln Pro Ala Arg Pro 85 90 95 Leu Gly Ser Ala Trp Arg AspGln Ser Gln Arg Pro Thr Ala Ser Ala 100 105 110 Arg Arg Arg Pro Ala ProAla Gly Ala Ala Pro Leu Thr Ala Val Ala 115 120 125 Pro Ala Pro Asp ThrAla Pro Val Pro Asp Val Asp Ser Arg Gly Ala 130 135 140 Ile Leu Arg ArgGln Tyr Asn Leu Ser Thr Ser Pro Leu Thr Ser Thr 145 150 155 160 Ile AlaThr Gly Thr Asn Leu Val Leu Tyr Ala Ala Pro Leu Ser Pro 165 170 175 LeuLeu Pro Leu Gln Asp Gly Thr Asn Thr His Ile Met Ala Thr Glu 180 185 190Ala Ser Asn Tyr Ala Gln Tyr Arg Val Val Arg Ala Thr Ile Arg Tyr 195 200205 Arg Pro Leu Val Pro Asn Ala Val Gly Gly Tyr Ala Ile Ser Ile Ser 210215 220 Phe Trp Pro Gln Thr Thr Thr Thr Pro Thr Ser Val Asp Met Asn Ser225 230 235 240 Ile Thr Ser Thr Asp Val Arg Ile Leu Val Gln Pro Gly IleAla Ser 245 250 255 Glu Leu Val Ile Pro Ser Glu Arg Leu His Tyr Arg AsnGln Gly Trp 260 265 270 Arg Ser Val Glu Thr Ser Gly Val Ala Glu Glu GluAla Thr Ser Gly 275 280 285 Leu Val Met Leu Cys Ile His Gly Ser Pro ValAsn Ser Tyr Thr Asn 290 295 300 Thr Pro Tyr Thr Gly Ala Leu Gly Leu LeuAsp Phe Ala Leu Glu Leu 305 310 315 320 Glu Phe Arg Asn Leu Thr Pro GlyAsn Thr Asn Thr Arg Val Ser Arg 325 330 335 Tyr Ser Ser Ser Ala Arg HisLys Leu Arg Arg Gly Pro Asp Gly Thr 340 345 350 Ala Glu Leu Thr Thr ThrAla Ala Thr Arg Phe Met Lys Asp Leu His 355 360 365 Phe Thr Gly Thr AsnGly Val Gly Glu Val Gly Arg Gly Ile Ala Leu 370 375 380 Thr Leu Phe AsnLeu Ala Asp Thr Leu Leu Gly Gly Leu Pro Thr Glu 385 390 395 400 Leu IleSer Ser Ala Gly Gly Gln Leu Phe Tyr Ser Arg Pro Val Val 405 410 415 SerAla Asn Gly Glu Pro Thr Val Lys Leu Tyr Thr Ser Val Glu Asn 420 425 430Ala Gln Gln Asp Lys Gly Ile Ala Ile Pro His Asp Ile Asp Leu Gly 435 440445 Glu Ser Arg Val Val Ile Gln Asp Tyr Asp Asn Gln His Glu Gln Asp 450455 460 Arg Pro Thr Pro Ser Pro Ala Pro Ser Arg Pro Phe Ser Val Leu Arg465 470 475 480 Ala Asn Asp Val Leu Trp Leu Ser Leu Thr Ala Ala Glu TyrAsp Gln 485 490 495 Thr Thr Tyr Gly Ser Ser Thr Asn Pro Met Tyr Val SerAsp Thr Val 500 505 510 Thr Phe Val Asn Val Ala Thr Gly Ala Gln Gly ValSer Arg Ser Leu 515 520 525 Asp Trp Ser Lys Val Thr Leu Asp Gly Arg ProLeu Thr Thr Ile Gln 530 535 540 Gln Tyr Ser Lys Thr Phe Phe Val Leu ProLeu Arg Gly Lys Leu Ser 545 550 555 560 Phe Trp Glu Ala Gly Thr Thr LysAla Gly Tyr Pro Tyr Asn Tyr Asn 565 570 575 Thr Thr Ala Ser Asp Gln IleLeu Ile Glu Asn Ala Ala Gly His Arg 580 585 590 Val Cys Ile Ser Thr TyrThr Thr Asn Leu Gly Ser Gly Pro Val Ser 595 600 605 Ile Ser Ala Val GlyVal Leu Ala Pro His Ser Ala Leu Ala Ala Leu 610 615 620 Glu Asp Thr ValAsp Tyr Pro Ala Arg Ala His Thr Phe Asp Asp Phe 625 630 635 640 Cys ProGlu Cys Arg Thr Leu Gly Leu Gln Gly Cys Ala Phe Gln Ser 645 650 655 ThrVal Ala Glu Leu Gln Arg Leu Lys Met Lys Val Gly Lys Thr Arg 660 665 670Glu Tyr 1/139

1. A polynucleotide probe including a sequence comprising at least eightnucleotides, the polynucleotide probe being used for detectingpolynucleotide of hepatitis E virus, characterized in that: (1) thesequence comprising at least eight nucleotides is hybridized with thepolynucleotide of the hepatitis E virus, thereby, due to thehybridization, detecting the hepatitis E virus; and (2) the sequencecomprising at least eight nucleotides is obtained from a sequenceselected from the group consisting of nucleotide sequences disclosed atSEQ No. 11, SEQ No. 44, SEQ No. 45, SEQ No. 46, SEQ No. 47 and SEQ No.48 and complementary strands thereof.
 2. A polynucleotide probeaccording to claim 1, wherein the sequence comprising at least eightnucleotides is obtained from a nucleotide sequence coding anon-structural protein and nucleocapside protein of HEV, orcomplementary strand thereof.
 3. A probe assay kit, including thepolynucleotide probe according to claim
 1. 4. A polynucleotide probeaccording to claim 1, wherein the sequence comprising at least eightnucleotides is selected from the group consisting of sequencesrepresented by a range from the 19^(th) nucleotide to the 37^(th)nucleotide of the SEQ No. 15, a range from the 52^(nd) nucleotide to the69^(th) nucleotide of SEQ No. 15, a range from the 77^(th) nucleotide tothe 95^(th) nucleotide of SEQ No. 15, a range from the 111^(th)nucleotide to the 127^(th) nucleotide of the SEQ No. 15, a range fromthe 174^(th) nucleotide to the 181^(st) nucleotide of the SEQ No. 15, arange from the 213^(th) nucleotide to the 220^(th) nucleotide of the SEQNo. 15 and a range from the 48^(th) nucleotide to the 100^(th)nucleotide of the SEQ No. 15 and complementary strands thereof.
 5. Apolynucleotide probe according to claim 1, wherein the hepatitis E viruscauses fulminant hepatitis E and the sequence comprising at least eightnucleotides selected in (2) according to claim 1 is obtained from anucleotide sequence disclosed at SEQ No.
 11. 6. A polynucleotide probeaccording to claim 1, wherein the hepatitis E virus is fulminanthepatitis E virus and the sequence comprising at least eight nucleotidesselected in (2) according to claim 1 is selected from the groupconsisting of nucleotide sequences disclosed at SEQ No. 9 and the SEQNo.
 10. 7. A method of detecting presence of hepatitis E virus in asample, comprising: (1) obtaining a sample from an object; (2) reactingthe sample obtained in the obtaining of (1) with the polynucleotideprobe according to claim 1; (3) detecting a double strand produced as aresult of the reaction of the reacting of (2); (4) determining whetheror not hepatitis E virus is present in the sample, on the basis of thedetection result of the detecting of (3).
 8. A method of detectingpresence of fulminant hepatitis E virus in a sample, comprising: (1)obtaining a sample from an object; (2) reacting the sample obtained inthe obtaining of (1) with the polynucleotide probe according to claim 6;(3) detecting a double strand produced as a result of the reaction ofthe reacting of (2); (4) determining whether or not hepatitis E virus ispresent in the sample, on the basis of the detection result of detectingof (3).
 9. A method of determining genotype of hepatitis E virus in asample, comprising: (1) reacting a sample with the polynucleotide probeaccording to claim 1; (2) detecting a double strand produced as a resultof the reaction of the reacting of (1); (3) determining genotype ofhepatitis E virus present in the sample, on the basis of the detectionresult of the detecting of (2).
 10. A chip for detecting a nucleotidesequence, on which the polynucleotide probe according to claim 1 hasbeen solid-phase fixed.
 11. A chip for detecting a nucleotide sequence,on which the polynucleotide probe according to claim 6 has beensolid-phase fixed.
 12. A pair or plural pairs of primer for PCR foramplifying polynucleotide of hepatitis E virus, the at least a pair ofprimer for PCR each independently having a sequence comprising at leasteight nucleotides, characterized in that: (1) the sequence comprising atleast eight nucleotides is hybridized with the polynucleotide of thehepatitis E virus, thereby, due to the hybridization, amplifying aportion of the polynucleotide of the hepatitis E virus; and (2) thesequence comprising at least eight nucleotides is obtained from asequence selected from the group consisting of nucleotide sequencesdisclosed at SEQ No. 11, SEQ No. 44, SEQ No. 45, SEQ No. 46, SEQ No. 47and SEQ No. 48 and complementary strands thereof.
 13. A pair or pluralpairs of primer for PCR according to claim 12, wherein the sequencecomprising at least eight nucleotides is obtained from a nucleotidesequence coding a nucleocapside protein of HCV, or complementary strandthereof.
 14. A PCR assay kit, including the pair or plural pairs ofprimer for PCR according to claim
 12. 15. A pair or plural pairs ofprimer for PCR according to claim 12, wherein the sequence comprising atleast eight nucleotides is selected from the group consisting ofsequences represented by a range from the 19^(th) nucleotide to the37^(th) nucleotide of the SEQ No. 15, a range from the 52^(nd)nucleotide to the 69^(th) nucleotide of SEQ No. 15, a range from the77^(th) nucleotide to the 95^(th) nucleotide of SEQ No. 15, a range fromthe 111^(th) nucleotide to the 127^(th) nucleotide of the SEQ No. 15, arange from the 174^(th) nucleotide to the 181^(st) nucleotide of the SEQNo. 15, a range from the 213^(th) nucleotide to the 220^(th) nucleotideof the SEQ No. 15 and a range from the 48^(th) nucleotide to the100^(th) nucleotide of the SEQ No. 15 and complementary strands thereof.16. A pair or plural pairs of primer for PCR according to claim 12,wherein the hepatitis E virus causes fulminant hepatitis E and thesequence comprising at least eight nucleotides selected in (2) accordingto claim 12 is obtained from a nucleotide sequence disclosed at SEQ No.11.
 17. A pair or plural pairs of primer for PCR according to claim 12,wherein the hepatitis E virus is fulminant hepatitis E virus and thesequence comprising at least eight nucleotides selected in (2) accordingto claim 12 is selected from the group consisting of nucleotidesequences disclosed at SEQ No. 9 and the SEQ No.
 10. 18. A method ofdetecting presence of hepatitis E virus in a sample, comprising: (1)obtaining a sample from an object; (2) reacting the sample obtained inthe obtaining of (1) with a pair of primer for PCR according to claim 12and polymerase, under a condition in which amplification is effected inan appropriate manner; (3) detecting presence of a product obtained as aresult of amplification by the reaction of the reacting of (2); (4)determining whether or not hepatitis E virus is present in the sample,on the basis of the detection result of the detecting of (3).
 19. Amethod of detecting presence of fulminant hepatitis E virus in a sample,comprising: (1) obtaining a sample from an object; (2) reacting thesample obtained in the obtaining of (1) with the at least a pair ofprimer for PCR according to claim 17 and polymerase, under a conditionin which amplification is effected in an appropriate manner; (3)detecting presence of a product obtained as a result of amplification bythe reaction of the reacting of (2); (4) determining whether or nothepatitis E virus is present in the sample, on the basis of thedetection result of the detecting of (3).
 20. A method of determininggenotype of hepatitis E virus in a sample, comprising: (1) reacting asample with a pair of primer for PCR according to claim 12 andpolymerase, under a condition in which amplification is effected in anappropriate manner; (2) determining length of a product obtained as aresult of amplification by the reaction of the reacting of (1); (3)determining genotype of hepatitis E virus present in the sample, on thebasis of the detection result of the detecting of (2).